Deep Vein Thrombosis Research: 2002-2006
  
Thromb Haemost. 2006 Oct;96(4):441-5.
Review on the value of graduated elastic compression stockings after deep vein thrombosis.
Kakkos SK, Daskalopoulou SS, Daskalopoulos ME, Nicolaides AN, Geroulakos G.
Department of Vascular Surgery, Faculty of Medicine, Imperial College London, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK. E-mail: g.geroulakos@imperial.ac.uk.

Graduated elastic compression stockings (GECS) are commonly used in the primary prevention of deep vein thrombosis (DVT); however, their role in preventing recurrent DVT and also post-thrombotic syndrome is less well established. The aim of this review was to investigate the effect of GECS after DVT. A literature search was performed by two independent searchers in order to identify randomised controlled trials on the effect of GECS in preventing recurrent DVT and post-thrombotic syndrome. Four randomised trials, including 537 patients, were identified. Two of the studies demonstrated that below-knee GECS significantly reduced post-thrombotic syndrome during follow-up, while a smaller study showed equivocal results. GECS reduced the incidence of post-thrombotic syndrome from 54% to 25.2% [relative risk (RR) 0.47, 95% confidence interval (CI) 0.36-0.61] with the number needed to treat (NNT) being 4 (95% CI 2.7-5.0). The rate of recurrent asymptomatic DVT was also significantly reduced by GECS (RR 0.20, 95% CI 0.06-0.64; NNT 5); the reduction in symptomatic DVT was not significant (RR 0.79, 95% CI 0.50-1.26; NNT 34). In conclusion, there is level Ia evidence to suggest that GECS can significantly reduce the incidence of post-thrombotic syndrome (PTS) after DVT, and therefore these should be routinely prescribed. The evidence for recurrent DVT is less conclusive. Further research is needed towards standardising PTS diagnostic criteria and evaluating more effective preventive measures after DVT.

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Thromb J. 2006 Sep 27;4(1):17 [Epub ahead of print]
Outcomes of thromboprophylaxis with enoxaparin vs. unfractionated heparin in medical inpatients: a retrospective database analysis.
McGarry LJ, Stokes ME, Thompson D.

ABSTRACT: BACKGROUND: Clinical trials have shown low-molecular weight heparin (LMWH) to be at least as safe and efficacious as unfractionated heparin (UFH) for preventing venous thromboembolism (VTE) in acutely-ill medical inpatients. The purpose of this study was to compare clinical and economic outcomes among medical inpatients receiving the LMWH enoxaparin versus UFH prophylaxis in real-world clinical practice. METHODS: Using a large, multi-hospital, US database, we identified persons aged [greater than or equal to]40 years hospitalized for [greater than or equal to]6 days for an acute medical condition (including circulatory disorders, respiratory disorders, infectious diseases, or neoplasms) from Q4 1999 to Q1 2002. From these patients, those who received thromboprophylaxis with either enoxaparin or UFH were identified. Surgical patients and those requiring or ineligible for anticoagulation were excluded. We compared the incidence of deep-vein thrombosis (DVT), pulmonary embolism (PE), and all VTE (i.e., DVT and/or PE). Secondary outcomes measures were occurrence of side-effects (major bleeds, thrombocytopenia), death in hospital, length of hospital stay and total costs. Categorical outcomes were compared using Chi2 statistics or Fischer's exact test; continuous measures were compared using Student's t-test. Propensity score methods were used to control for confounding and sensitivity analyses performed to examine the effect of misclassification of treatment and outcome on results. RESULTS: We identified 479 patients receiving enoxaparin prophylaxis and 2,837 receiving UFH. The incidence of VTE was 1.7% among enoxaparin patients versus 6.3% among those receiving UFH (RR=0.26; p<0.001). Occurrence of major bleeds (2.5% with enoxaparin vs. 2.5% with UFH; p=0. 966) and death in hospital (5.2% vs. 5.0%; p=0.843) were similar; there were no recorded cases of thrombocytopenia. Length of stay in hospital (10.00 days with enoxaparin vs. 10.26 days with UFH; p=0.348) and total inpatient costs ($18,777 vs. $17,602; p=0.463) also were similar in the 2 groups. Adjusted analyses and sensitivity analyses yielded similar results. CONCLUSION: We observed a 74% lower risk of VTE among patients receiving enoxaparin prophylaxis versus UFH prophylaxis. There was no significant difference in side-effects, death in hospital, or economic outcomes. These results provide evidence that the LMWH enoxaparin is more effective than UFH in reducing the risk of VTE in real-world clinical practice.

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J Gen Intern Med. 2006 Sep 25; [Epub ahead of print]
BRIEF REPORT: Graduated Compression Stocking Thromboprophylaxis for Elderly Inpatients: A Propensity Analysis.
Labarere J, Bosson JL, Sevestre MA, Delmas AS, Dupas S, Thenault MH, Legagneux A, Boge G, Terriat B, Pernod G; On behalf of the Association pour la Promotion de l'Angiologie Hospitaliere.
ThEMAS TIMC-IMAG UMR CNRS 5525 UJF, Grenoble, France.

BACKGROUND: Graduated compression stockings (GCS) are often used for deep vein thrombosis prophylaxis in nonsurgical patients, although evidence on their effectiveness is lacking in this setting. OBJECTIVE: To determine whether prophylaxis with GCS is associated with a decrease in the rate of deep vein thrombosis in nonsurgical elderly patients. METHODS: Using original data from 2 multicenter nonrandomized studies, we performed multivariable and propensity score analyses to determine whether prophylaxis with GCS reduced the rate of deep vein thrombosis among 1,310 postacute care patients 65 years or older. The primary outcome was proximal deep vein thrombosis detected by routine compression ultrasonography performed by registered vascular physicians. RESULTS: Proximal deep vein thrombosis was found in 5.7% (21/371) of the GCS users and in 5.2% (49/939) of the GCS nonusers (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.64-1.84). Although adjusting for propensity score eliminated all differences in baseline characteristics between users and nonusers, the OR for proximal deep vein thrombosis associated with GCS remained nonsignificant in propensity-stratified (adjusted OR, 1.11; 95% CI, 0.59-2.10) and propensity-matched (conditional OR, 0.92; 95% CI, 0.42-2.02) analysis. Similar figures were observed for distal and any deep vein thrombosis. The rates of deep vein thrombosis did not differ according to the length of stockings. CONCLUSIONS: Prophylaxis with GCS is not associated with a lower rate of deep vein thrombosis in nonsurgical elderly patients in routine practice. Randomized studies are needed to assess the efficacy of GCS when properly used in this setting.

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Cardiovasc Intervent Radiol. 2006 Sep 11; [Epub ahead of print]
Catheter-Directed Thrombolysis with Percutaneous Rheolytic Thrombectomy Versus Thrombolysis Alone in Upper and Lower Extremity Deep Vein Thrombosis.
Kim HS, Patra A, Paxton BE, Khan J, Streiff MB.
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

PURPOSE: To compare the efficacy of catheter-directed thrombolysis (CDT) alone versus CDT with rheolytic percutaneous mechanical thrombectomy (PMT) for upper and lower extremity deep vein thrombosis (DVT). METHODS: A retrospective cohort of consecutive patients with acute iliofemoral or brachiosubclavian DVT treated with urokinase CDT was identified, and a chart review was conducted. Demographic characteristics, treatment duration, total lytic dose, clot lysis rates and complications were compared in patients treated with urokinase CDT alone or combined CDT and rheolytic PMT. RESULTS: Forty limbs in 36 patients were treated with urokinase CDT alone. Twenty-seven limbs in 21 patients were treated with urokinase CDT and rheolytic PMT. The mean treatment duration for urokinase CDT alone was 48.0 +/- 27.1 hr compared with 26.3 +/- 16.6 hr for urokinase CDT and rheolytic PMT (p = 0.0004). The mean urokinase dose required for CDT alone was 5.6 +/- 5.3 million units compared with 2.7 +/- 1.8 million units for urokinase CDT with rheolytic PMT (p = 0.008). Complete clot lysis was achieved in 73% (29/40) of DVT treated with urokinase CDT alone compared with 82% (22/27) treated with urokinase CDT with rheolytic PMT. CONCLUSION: Percutaneous CDT with rheolytic PMT is as effective as CDT alone for acute proximal extremity DVT but requires significantly shorter treatment duration and lower lytic doses. Randomized studies to confirm the benefits of pharmacomechanical thrombolysis in the treatment of acute proximal extremity DVT are warranted.

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Plast Surg Nurs. 2006 July/September;26(3):164-168.
Prevention and Management of Deep Vein Thrombosis and Pulmonary Embolism in Plastic Surgery.
Sagrillo DP, Kunz S.
Dawn P. Sagrillo, BSN, RN, CPSN, is Vice President of Aesthetic Advancement, Inc., Atlanta, GA, and an Aesthetic Nurse Specialist, Aesthetic and Reconstructive Surgery Associates, Waukesha, WI. Sue Kunz, BS, RN, CPSN, is in practice at the Clinic of Cosmetic Surgery, Milwaukee, WI.

A phrase commonly stated in plastic surgery is that if a surgeon has no complications, than he or she is performing no surgery. Those of us who have practiced in the surgical arena are fully aware that adverse events can happen after the most minor of surgical procedures. It is the prevention of complications that ultimately defines surgeons' responsibility to their patients. In elective, aesthetic surgery, this expectation is even greater as patients generally present healthy, have high hopes, and have a low tolerance for any unexpected problem.Thromboembolism is a feared complication of surgery across many disciplines, including plastic surgery. Deep vein thombosis (DVT) and pulmonary embolism (PE) can result in significant morbidity, even death. The overall incidence of DVT in the United States is 84-150 per 100,000 per year. The incidence of PE in the United States has a wide reported range, from 125,000 to 400,000 cases per year. Pulmonary embolism is responsible for about 150,000 deaths per year and is reported to be the third most common direct cause of death in the United States. Pulmonary embolism results in approximately 5% of all perioperative deaths. However, if diagnosed and treated early, PE carries a mortality rate of 2% to 8% (). The American Society of Plastic Surgeons (ASPS) reported in 2001 that an estimated more than 18,000 cases of DVT may occur in patients undergoing plastic surgery each year ().As we focus this issue on safety in plastic surgery, we felt this was an important and timely topic to address in Journal Club. We hope you will find these articles beneficial resources in educating you and guiding your protocols for patient safety within your aesthetic surgical practice.

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Clin Orthop Relat Res. 2006 Aug 31; [Epub ahead of print]
The Benefit of Aspirin Chemoprophylaxis for Thromboembolism after Total Knee Arthroplasty.
Lotke PA, Lonner JH.
>From the *Hospital of the University of Pennsylvania, Philadelphia, PA and the Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA; and daggerBooth Bartolozzi Balderston Orthopaedics, Philadelphia, PA.

The threat of thromboembolic events after total knee arthroplasty has been substantially reduced during the past decade. Currently, the risk of fatal pulmonary embolism is approximately 0.1%. This is due to a confluence of changes in our medical practices, including early mobilization, less traumatic surgery, increased use of regional anesthesia, pneumatic compression devices, and chemoprophylactic agents. Because many chemoprophylactic agents are associated with an increased risk of bleeding, we have chosen aspirin as our preferred method of chemoprophylaxis. This study seeks to determine if aspirin is as effective as newer chemoprophylactic agents as judged by the prevalence of fatal or nonfatal pulmonary embolus, readmission for deep venous thrombosis, and risk of bleeding. Aspirin was the principle chemoprophylactic agent for 3473 consecutive patients having total knee arthroplasty. All patients were followed for a minimum of 6 weeks. There were nine deaths: two from pulmonary embolism, five cardiac events, one stroke, and one fat embolism. Three cardiac-related deaths occurred in patients for whom pulmonary embolism could not definitively be ruled out. Therefore, the best case and worst case scenarios for fatal pulmonary embolism were 0.06% and 0.14%, respectively. Thirteen patients underwent reoperation for hematoma (0.4%). Therefore, we have demonstrated aspirin combined with early mobilization, regional anesthesia, foot pumps, and improved surgical techniques is safer than and equally efficacious as other chemoprophylaxis agents.Level of Evidence: Level IV, Therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

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Thromb Res. 2006 May 2; [Epub ahead of print]
What is the optimal pharmacological prophylaxis for the prevention of deep-vein thrombosis and pulmonary embolism in patients with acute ischemic stroke?
Kamphuisen PW, Agnelli G.
Stroke Unit and Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy; Division of Vascular Medicine, Department of Internal Medicine, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.

BACKGROUND: Pulmonary embolism after acute ischemic stroke (AIS) is associated with a high in-hospital mortality. The benefit from pharmacological prophylaxis for venous thromboembolism (VTE) is uncertain probably due to doubts about the optimal agent and dose. We evaluated the benefit/risk ratio of different anticoagulant regimens in the prevention of VTE in patients with AIS. METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were searched up to January 2005. Randomized controlled trials (RCT) comparing early administration of either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) with control were included. Endpoints were objectively diagnosed deep-vein thrombosis (DVT), pulmonary embolism, intracranial hemorrhage (ICH), and extracranial hemorrhage (ECH). Low-dose UFH was arbitrarily defined as </=15,000 IU/day, low-dose LMWH as </=6000 IU/day or weight-adjusted dose of </=86 IU/kg/day. RESULTS: Sixteen trials involving 23,043 patients with AIS met the inclusion criteria. The number of events was small and different doses of anticoagulant treatment were used. Compared to control, high-dose UFH was associated with a reduction in pulmonary embolism (OR=0.49, 95% confidence interval (CI)=0.29-0.83), but also with an increased risk of ICH (OR=3.86, 95% CI=2.41-6.19) and ECH (OR=4.74, 95% CI=2.88-7.78). Low-dose UFH decreased the thrombosis risk (OR=0.17, 95% CI=0.11-0.26), but had no influence on pulmonary embolism (OR=0.83, 95% CI=0.53-1.31); the risk of ICH or ECH was not statistically significant increased (OR=1.67, 95% CI=0.97-2.87 for ICH; and OR=1.58, 95% CI=0.89-2.81 for ECH, respectively). High-dose LMWH decreased both DVT (OR=0.07, 95% CI=0.02-0.29) and pulmonary embolism (0.44, 95% CI=0.18-1.11), but this benefit was offset by an increased risk for ICH (OR=2.01, 95% CI=1.02-3.96) and ECH (OR=1.78, 95% CI=0.99-3.17). Low-dose LMWH reduced the incidence of both DVT (OR=0.34, 95% CI=0.19-0.59) and pulmonary embolism (OR=0.36, 95% CI=0.15-0.87), without an increased risk of ICH (OR=1.39, 95% CI=0.53-3.67) or ECH (OR=1.44, 95% CI=0.13-16). For low-dose LMWH, the numbers needed to treat were 7 and 38 for DVT and pulmonary embolism, respectively. CONCLUSIONS: Indirect comparison of low and high doses of UFH and LMWH suggests that low-dose LMWH have the best benefit/risk ratio in patients with acute ischemic stroke by decreasing the risk of both DVT and pulmonary embolism, without a clear increase in ICH or ECH.

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Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004002.
Compression stockings for preventing deep vein thrombosis in airline passengers.
Clarke M, Hopewell S, Juszczak E, Eisinga A, Kjeldstrom M.

BACKGROUND: Air travel might increase the risk of deep vein thrombosis (DVT). It has been suggested that wearing compression stockings might reduce this risk. OBJECTIVES: To assess the effects of wearing compression stockings versus not wearing them among people travelling on flights lasting at least four hours. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group's Specialized Register (January 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library, Issue 4, 2005), MEDLINE (January 1966 to November 2005), EMBASE (January 1980 to December 2005) and several other electronic or grey literature sources, detailed in full in the review. The most recent searches were done in January 2006. SELECTION CRITERIA: Randomized trials of compression stockings versus no stockings in passengers on flights lasting at least four hours. Trials in which passengers wore a stocking on one leg but not the other, or those comparing stockings and another intervention were also eligible. DATA COLLECTION AND ANALYSIS: At least two authors independently assessed the quality of each study and extracted data. We sought additional information from trialists. MAIN RESULTS: Ten randomized trials (n = 2856) were included; nine (n = 2821) compared wearing stockings on both legs versus not wearing them, and one (n = 35) compared wearing a stocking on one leg for the outbound flight and on the other leg on the return flight. Of the nine trials, seven included people judged to be at low or medium risk (n = 1548) and two included high risk participants (n = 1273). All flights lasted at least seven hours.Fifty of 2637 participants with follow-up data available in the trials of wearing stockings on both legs had a symptomless DVT; three wore stockings, 47 did not (odds ratio 0.10, 95% confidence interval 0.04 to 0.25, P < 0.00001). There were no symptomless DVTs in three trials. No deaths, pulmonary emboli or symptomatic DVTs were reported. Wearing stockings had a significant impact in reducing oedema (based on six trials). No significant adverse effects were reported. AUTHORS' CONCLUSIONS: Airline passengers similar to those in this review can expect a substantial reduction in the incidence of symptomless DVT and leg oedema if they wear compression stockings. We cannot assess the effect of wearing stockings on death, pulmonary embolus or symptomatic DVT because no such events occurred in these trials. Randomized trials to assess these outcomes would need to include a very large number of people.

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Curr Med Res Opin. 2006 Mar;22(3):593-602.
Mobilization versus immobilization in the treatment of acute proximal deep venous thrombosis: a prospective, randomized, open, multicentre trial.
Junger M, Diehm C, Storiko H, Hach-Wunderle V, Heidrich H, Karasch T, Ochs HR, Ranft J, Sannwald GA, Strolin A, Janssen D.
Clinic and Policlinic for Dermatology, Ernst-Moritz-Arndt-University Greifswald, 17487 Greifswald, Germany. juenger@uni-greifswald.de

OBJECTIVE: The aim of prescribing strict bed rest for acute deep venous thrombosis is to reduce the risk of pulmonary embolism and pain in the legs, as well as swelling. This study was performed in order to compare outcome of mobilization against 5 days of strict bed rest in patients with acute proximal deep venous thrombosis (DVT). METHODS: 103 in-patients with proximal DVT or patients admitted to the hospital because of proximal DVT were recruited to a randomized study. All patients were treated in hospital and given a lower leg and thigh compression bandage as well as therapeutic doses of the low molecular weight heparin, dalteparin-sodium (Fragmin). RESULTS: Seven of 52 patients (13.5%) in the mobile group versus 14 of 50 patients (28.0%) in the immobile group suffered at least one of the outcomes defined under the combined primary endpoint (clinically relevant pulmonary embolisms, pulmonary embolisms detectable by scintigraphy or computer tomography, progression of thrombosis or new thrombosis, nosocomial infections and/or serious adverse events) (p = 0.088), whereby serious adverse events occurred once in the mobile group and three times in the immobile group. New pulmonary embolisms over the course were seen in 10 of 50 patients (20%) with a perfusion disorder at baseline scintigraphy, while such was ascertained only in one of 52 patients (1.9%) without a perfusion disorder at baseline scintigraphy. Leg pain was reduced from 54.1 (+/-30.4) to 20.7 (+/-19.2) in the mobilized group and from 41.0 (+/-26.8) to 14.0 (+/-11.1) in the immobilized patients. Leg pain was assessed using the visual analogue scale (0 = no pain, 100 = maximum pain). More immobilized patients complained of increasing back pain (23% versus 6%) and disturbed micturition (10% versus 2%) as well as defecation (13% versus 6%) on day 5. More patients in the mobile group reported increased stress from the thrombosis and its treatment (15% versus 6%). CONCLUSIONS: No benefit of prescribing bed rest in patients with deep venous thrombosis could be detected in this study. Based on data available, strict bed rest for at least 5 days is not justified if adequate therapy with low molecular weight heparin and adequate compression is assured. It remains open whether patients with initial signs of pulmonary embolism might profit from a brief immobilization.

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Bull Cancer. 2006 Mar 1;93(3):271-81.
[Treatment of venous thrombosis in cancer patients: practical aspects]
[Article in French]
Laza-Achille M, Desruennes E, Di Palma M.
Departement de medecine adulte, Institut Gustave Roussy, 39, rue Camille-Desmoulin, 94800 Villejuif. mihaela_laza@yahoo.com

The risk of venous thromboembolism (VTE) is increased in association with malignancy, and has a potential to produce significant morbidity and mortality. Treatment of such patients with anticoagulants is associated with both benefit and a high rate of complications. In the early phase, the treatment is usually achieved with low molecular weight heparin (LMWH), which has a number of advantages over unfractionated heparin (UFH): once or twice daily administration, no necessary laboratory monitoring, lesser risk of bleeding and no drugs interactions. Nevertheless, the UFH is the anticoagulant of choice when a rapid anticoagulant effect or stop of anticoagulant effect is required, in the treatment of massive pulmonary embolism or severe renal insufficiency. Prolonged anticoagulation with LMWH (over 3 or 6 months) appears to be beneficial on survival for such patients. The subject of anticoagulation in patients with primary or secondary brain tumours is controversial. The long-term anticoagulation mainly use LMWH or vitamin K antagonist. The last ones are more difficult to use because of an unpredictable response with higher rate of recurrence and bleeding. The optimal duration of treatment is not known but the patients should be treated for at least 6 months, even at least 12 months after a second episode of venous thromboembolism. On the primary prevention in high-risk surgical oncology, the LMWH are at least as effective and safer as UFH when the optimal dose was administered. For the medical patients, the use of prophylactic anticoagulant treatment is less clear except the patients who are bedridden for prolonged periods of time. For the secondary prevention, the LMWH seems to be more effective over vitamin K antagonists. For these patients, the anticoagulant therapy is recommended indefinitely or until cancer is resolved.

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Cardiovasc Drug Rev. 2005 Winter;23(4):331-44.
Ximelagatran, the new oral anticoagulant: would warfarin survive the challenge?
Mousa SA, Abdel-Razeq HN.
The Pharmaceutical Research Institute, 106 New Scotland Avenue, Albany, NY 12208, USA. mousas@acp.edu.

The last decade witnessed major advances in the prevention and treatment of venous as well as of arterial thrombosis. Limitations of existing anticoagulants led to the development of novel therapeutic approaches. Ximelagatran is a new direct thrombin inhibitor (DTI) that is given orally, without the need for close monitoring. This compound was tried in the treatment of active venous thromboembolism, and the results were encouraging. Randomized trials suggest that ximelagatran is not inferior to warfarin in the prevention of stroke in patients with nonvalvular atrial fibrillation. Multiple controlled, prospective trials compared ximelagatran with low molecular weight heparin or warfarin in prevention of venous thromboembolism in patients undergoing major orthopedic procedures. The results of these clinical trials are reviewed in this article. Because of certain safety concerns (increased liver enzymes, potential hepatonecrosis, and increased coronary events) ximelagatran has not yet been approved by the FDA. Additional studies may be required to address these concerns. Ximelagatran has been approved, however, by the European regulatory authorities for short-term thromboprophylaxis. The success of ximelagatran or other oral antithrombin agents would provide significant proof of the concept for the long-term use of oral antithrombins in the prevention and treatment of both arterial and venous thrombosis.

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Curr Opin Anaesthesiol. 2006 Feb;19(1):52-8.
Update in the prevention and treatment of deep vein thrombosis and pulmonary embolism.
Motsch J, Walther A, Bock M, Bottiger BW.
Department of Anaesthesiology and Intensive Care, Thoracic Clinic, University Heidelberg, Heidelberg, Germany. johann.motsch@med.uni-heidelburg.de

PURPOSE OF REVIEW: Thromboembolic events have a major impact on outcome of surgical and medical patients. This review is focused on standards and recent advances in antithrombotic strategies for prevention and therapy of venous thromboembolism and pulmonary embolism. RECENT FINDINGS: Alert programs improve prophylactic strategies to prevent venous thromboembolism. Evidenced-based guidelines are available on antithrombotic and thrombolytic therapy outweighing the benefits, risks, burdens and costs. Selective factor Xa and direct thrombin inhibitors are at least as effective as low-molecular-weight heparin in prevention of venous thromboembolism and treatment of pulmonary embolism, but have fewer side effects and will not need routine monitoring. In high-risk orthopaedic patients but not in general surgery patients fondaparinux is superior to low-molecular-weight heparin in the prevention of thromboembolic disease. Ximelagatran, the first oral direct thrombin inhibitor, is as effective and well tolerated as warfarin. Long-term treatment is uncertain, however, because of elevation in alanine transaminase levels. In high-risk patients with contraindication for anticoagulation, retrievable vena cava filters may be an option to prevent pulmonary embolism. Permanent cava filters do not improve long-term survival and are associated with relevant side effects. Thrombolytics should be reserved for deep venous thrombosis complicated by limb gangrene and for life threatening pulmonary embolism. SUMMARY: There is currently sufficient information based on guidelines available on preventive and therapeutic strategies for venous thromboembolism and pulmonary embolism. Antithrombotics are the therapeutic backbone. In high-risk orthopedic surgery and venous thromboembolism the new antithrombotics fondaparinux, idraparinux and ximelagatran are superior to standard treatment. Temporary caval filters may be a therapeutic option in high-risk patients with contraindication for antithrombotics.

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Gend Med. 2005;2 Suppl A:S10-7.
Venous thromboembolism and anticoagulant therapy in pregnancy.
Greer IA.
University of Glasgow, Division of Developmental Medicine, Maternal and Reproductive Medicine, Glasgow Royal Infirmary, Scotland, UK. I.A.Greer@clinmed.gla.ac.uk

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of maternal mortality in western countries. Many of these deaths could be prevented by optimal prophylaxis and management. OBJECTIVE: The aim of this study was to examine the current literature to assess the risk of VTE in pregnant women and to identify the most effective and safe anticoagulant therapy. METHODS: A search was conducted using the major electronic databases of PubMed and MEDLINE 1996-October 2005 using the following key words: Pregnancy, venous thrombosis, thrombophilia, prosthetic heart valves, anticoagulants, heparin, low-molecular-weight heparin, coumarin, and warfarin. RESULTS: The common risk factors for VTE during pregnancy are age >35 years, obesity, operative delivery, thrombophilia, and a family or personal history of VTE. Coumarins are unsuitable for use during pregnancy because of embryopathy and risk of fetal bleeding. Low-molecular-weight heparins (LMWHs), such as enoxaparin and dalteparin, are safer and more convenient than unfractionated heparin (UFH). LMWH is now the agent of choice for pharmacologic thromboprophylaxis and treatment of VTE during pregnancy. Women with a suspected VTE should receive anticoagulant therapy until an objective diagnostic test is performed, unless there is a clear contraindication to anticoagulation. If a VTE is confirmed, anticoagulant treatment should be continued throughout pregnancy. These patients usually, require at least 6 months of anticoagulation, and treatment should be continued until at least 6 weeks postpartum. Management of women with prosthetic heart valves in pregnancy is controversial; while coumarin treatment is more effective than UFH for thromboprophylaxis in the mother, UFH is associated with a better outcome for the fetus. Coumarin embryopathy can be avoided if heparin is substituted by 6 weeks' gestation. The limited data on LMWH in women with prosthetic heart valves suggest that it compares favorably with UFH. CONCLUSIONS: LMWH is now the anticoagulant of choice for the treatment and prevention of VTE in pregnancy. However, the management of women with prosthetic heart valves requiring anticoagulation in pregnancy remains controversial as coumarins appear safer for the mother, but heparin is associated with less fetal morbidity and data on LMWH are limited.

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J Bone Joint Surg Am. 2006 Feb;88-A(2):261-266.
Prophylaxis Against Deep-Vein Thrombosis Following Trauma: A Prospective, Randomized Comparison of Mechanical and Pharmacologic Prophylaxis.
Stannard JP, Lopez-Ben RR, Volgas DA, Anderson ER, Busbee M, Karr DK, McGwin GR Jr, Alonso JE.
Division of Orthopaedic Surgery, University of Alabama at Birmingham, 509 Medical Education Building, 619 South 19th Street, Birmingham, AL 35294-3295. james.stannard@ortho.uab.edu.

BACKGROUND: Deep-vein thrombosis following skeletal trauma is an important yet poorly studied issue. The purpose of the present study was to evaluate the efficacy of two different strategies for prophylaxis against deep-vein thrombosis and pulmonary embolus following blunt skeletal trauma. METHODS: Two hundred and twenty-four inpatients were enrolled in a prospective, randomized study investigating venous thromboembolic disease following trauma. Two hundred patients completed the study, which compared two different regimens of prophylaxis. The patients in Group A received enoxaparin (30 mg, administered subcutaneously twice a day) starting twenty-four to forty-eight hours after blunt trauma. The patients in Group B were managed with pulsatile foot pumps at the time of admission combined with enoxaparin on a delayed basis. All patients were screened with magnetic resonance venography and ultrasonography before discharge. RESULTS: There were ninety-seven patients in Group A and 103 patients in Group B. Twenty-two patients (including thirteen in Group A and nine in Group B) had development of deep-vein thrombosis, with two (both in Group A) also having development of pulmonary embolism. The prevalence of deep-vein thrombosis was 11% for the whole series, 13.4% for Group A, and 8.7% for Group B; the difference between Groups A and B was not significant. There were eleven large or occlusive clots (prevalence, 11.3%) in Group A, compared with only three (prevalence, 2.9%) in Group B (p = 0.025). The prevalence of pulmonary embolism was 2.1% in Group A and 0% in Group B. Wound complications occurred in twenty-one patients in Group A, compared with twenty patients in Group B. Patients who had development of deep-vein thrombosis during the inpatient portion of the study required a mean of 7.4 units of blood during hospitalization, compared with 3.9 units of blood for those who did not (p < 0.05). CONCLUSIONS: Our results indicate that early mechanical prophylaxis with foot pumps and the addition of enoxaparin on a delayed basis is a very successful strategy for prophylaxis against venous thromboembolic disease following serious musculoskeletal injury. The prevalence of large or occlusive deep-vein thromboses among patients who had been managed with this protocol was significantly less than that among patients who had been managed with enoxaparin alone. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

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Angiology. 2006 Jan-Feb;57(1):53-64.
A study on the safety, efficacy, and efficiency of sulodexide compared with acenocoumarol in secondary prophylaxis in patients with deep venous thrombosis.
Cirujeda JL, Granado PC.
Hematology Department, San Millan Hospital Complex, San Pedro Logrono (La Rioja), Madrid, Spain. med005333@saludalia.com.

This study was carried out to study the safety and efficacy of a fixed dosage of sulodexide compared to adjusted dosages (INR) of acenocoumarol as secondary prophylaxis in patients with deep vein thrombosis (DVT) in lower limbs. An economic evaluation based on the criteria of use in normal clinical practice was also performed. One hundred and fifty patients of both sexes were included, all over 18 years of age and diagnosed with proximal DVT of the lower limbs by color echo-Doppler, and with clinical evolution of less than 1 month. The patients were initially treated with low-molecular-weight heparin (LMWH) and urokinase in accordance with the established protocol. They were then randomized to continue treatment with acenocoumarol and INR adjustments every 30 days, or with sulodexide. Treatment was extended for 3 months with monthly follow-up visits and a final visit at 3 months posttreatment. No differences between the groups were detected concerning demographic or basal characteristics in clinical evolution or adverse reactions. In the group treated with sulodexide, no major/minor hemorrhagic complications were detected. On the other hand, in the acenocoumarol group, 1 major hemorrhage and 9 minor hemorrhages were produced (13.3%), reaching statistical difference in relation to the sulodexide group (p = 0.014; CI from 95% of 4.7% to 19.4%). Regarding the economic impact, treatment costs with sulodexide are much less than those with acenocoumarol, the data confirmed by the sensitivity analyses performed. The results prove the efficacy, safety, and efficiency of sulodexide as a secondary prophylaxis in thromboembolic disease, avoiding hemorrhagic risks and the monitoring of patients, and providing significant savings to the health system.

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J Manag Care Pharm. 2006 Jan-Feb;12(1):70-5.
A pilot study of home treatment of deep vein thrombosis with subcutaneous once-daily enoxaparin plus warfarin.
Bishop B, Wilson AG, Post D, Howard L, Ruehlen L.
Saint Joseph's Health System, 15855 Nineteen Mile Rd., Clinton Township, MI, 48038, USA. bishobp@trinity-health.org.

OBJECTIVE: To evaluate patient satisfaction, effectiveness, and safety of at-home treatment of acute deep vein thrombosis (DVT) with subcutaneous enoxaparin dosed at 1.5 mg/kg once daily plus oral warfarin. METHODS: Patients with acute DVT and no more than 1 previous episode of DVT received enoxaparin plus oral warfarin until their international normalized ratio (INR) was >2 on 2 consecutive days. Patients were recruited between November 2000 and June 2003, and a home-care nurse visited the patient daily to administer the enoxaparin and to perform a fingerstick INR test. Patients received warfarin at doses adjusted to maintain an INR in the range of 2 to 3. Efficacy and safety were assessed daily by a home-care nurse and then by telephone interview conducted by a pharmacist at 14, 30, and 90 days during follow-up. Patient satisfaction with treatment was assessed by a verbal questionnaire. RESULTS: There were 52 patients enrolled. The mean duration of enoxaparin home treatment was 4.5 days, and the mean INR on discontinuation of enoxaparin was 2.73. Most patients (84.6%) had INRs within the desired therapeutic range (INR value 2-3); no patient had a subtherapeutic INR. There were no symptoms of recurrent venous thromboembolism reported. Major bleeding occurred 7 days after discontinuation of enoxaparin in one patient with impending surgery for removal of a uterine tumor. There were 2 cases of minor bleeding. The patient satisfaction questionnaire revealed that patients considered home treatment to be acceptable. The average cost savings was $2,925 per patient compared with typical inpatient treatment with unfractionated heparin. CONCLUSION: The results of this pilot study suggest that home treatment with initial once-daily enoxaparin in conjunction with long-term oral warfarin is a safe and effective alternative to inpatient therapy with once-daily enoxaparin or unfractionated heparin for select patients with acute DVT. Cost savings are derived from the substitution of inpatient care with home care.

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Hamostaseologie. 2006;26(1):63-71.
Pregnancy-associated venous thromboembolic disease: prediction, prevention, and therapy.
Zotz RB, Gerhardt A, Scharf RE.
Institut fur Hamostaseologie und Transfusionsmedizin, Universitatsklinikum Dusseldorf, Moorenstrasse 5, 40225 Dusseldorf, E-Mail: zotz@med.uni-duesseldorf.de.

Thromboembolic disease remains a leading cause of maternal mortality during pregnancy and the puerperium. Rational and risk-adapted administration of heparin prophylaxis depends on 1. the identification of those women who have an increased risk of thrombosis and 2. the accurate quantification of this risk. In women without prior thrombosis, the presence of a heterozygous factor V Leiden or heterozygous G20210A mutation in the prothrombin gene is associated with a pregnancy-associated thrombotic risk of approximately 1 in 400. Thus, in pregnant carriers of either one of these mutations the risk of venous thromboembolism is low. Therefore, no heparin prophylaxis is recommended. A combination of the two genetic risk factors can increase the risk to a modest level of 1 in 25. In women with a single episode of prior thrombosis associated with a transient risk factor, e.g. surgery or trauma, and no additional genetic risk factor, the probability of a pregnancy-associated thrombosis appears also to be low. However, data are sparse and conflicting. In contrast, in women with a prior idiopathic venous thrombosis who carry an additional hereditary risk factor or who have a positive family history of thrombosis, a high risk (>10%) can be expected supporting the indication for active antepartum and postpartum heparin prophylaxis. Despite the remarkable progress in risk stratification, the absolute magnitude of risk and the optimal management in many cases is an issue of ongoing debate.

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Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003746.
Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism.
Cundiff D, Manyemba J, Pezzullo J.

BACKGROUND: Venous thromboembolism (VTE) is the term given to any thromboembolic event (blocking of a blood vessel by a blood clot) occurring in the venous system. The current treatment recommended for VTE is anticoagulation (reduction of the blood's ability to clot). The aim of this review is to summarize results from randomized controlled trials (RCTs) for the effectiveness of anticoagulants (heparins, including low molecular weight heparins and vitamin K antagonists) in the treatment of VTE, compared to non-steroidal anti-inflammatory drugs (NSAIDs) or placebo. OBJECTIVES: To examine the randomized controlled evidence for the effectiveness and safety of anticoagulant treatment compared to NSAIDs or placebo in patients with VTE on the incidence of fatal and non-fatal pulmonary emboli (PE) and the recurrence or extension of deep vein thrombosis (DVT). SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialized Trials Register (last searched 26 July 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL) database (last searched Issue 3, 2005). In addition, DKC also searched reference lists and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: All randomized trials of anticoagulants versus NSAIDs or placebo in the initial treatment of VTE (DVT or PE or both). DATA COLLECTION AND ANALYSIS: DKC and JM independently assessed trial quality and extracted data. JCP (biostatistician) analyzed the design elements and feasibility of a future randomized controlled trial to determine definitively efficacy and safety of anticoagulants in VTE treatment. MAIN RESULTS: Two RCTs were included. Data were not pooled because of heterogeneity between the studies. The two RCTs were too small to determine any difference in mortality, occurrence of pulmonary emboli, progression or return of DVT between patients treated with anticoagulation and those receiving no anticoagulation. AUTHORS' CONCLUSIONS: The limited evidence from RCTs of anticoagulants versus NSAIDs or placebo is inconclusive regarding the efficacy and safety of anticoagulants in VTE treatment. The use of anticoagulants is widely accepted in clinical practice, so a further RCT comparing anticoagulants to placebo could not ethically be carried out.

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Gynecol Oncol. 2006 Jan 5; [Epub ahead of print]
Low-dose warfarin does not decrease the rate of thrombosis in patients with cervix and vulvo-vaginal cancer treated with chemotherapy, radiation, and erythropoeitin.
Lin A, Ryu J, Harvey D, Sieracki B, Scudder S, Wun T.
Department of Internal Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA.

OBJECTIVES.: We had previously reported an association between the use of recombinant human erythropoietin (rHuEPO) and thrombosis in patients with cervix and vulvo-vaginal cancer treated with chemotherapy and radiation. We hypothesized that low-dose warfarin would be effective prevention for thromboembolic events in this setting. METHODS.: A retrospective analysis of patients with cervical or vulvo-vaginal carcinoma receiving chemoradiation and rHuEpo was performed. Thirty-two patients received rHuEpo alone, and 24 received warfarin (1-2 mg) and rHuEpo. The primary endpoint was objectively proven symptomatic venous thrombosis. RESULTS.: There was no difference in the baseline characteristics (e.g. age, stage, body mass index, mean and peak hemoglobin, WBC and platelet counts, and number of transfusions) between these two groups. The rate of thrombosis also was not statistically different (P = 0.62). Nine of 24 patients had a symptomatic deep vein thrombosis (DVT) while receiving warfarin compared to 10 of 32 patients not on warfarin. There was no difference between the two groups in the percentage of patients with upper extremity DVT (P = 0.83) or lower extremity DVT (P = 0.64). CONCLUSION.: Daily low-dose warfarin did not alter the incidence of symptomatic DVT in patients with cervical or vulvo-vaginal cancer who received rHuEpo in conjunction with chemoradiation.

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Thromb Haemost. 2005 Dec;94(6):1181-5.
Intermittent pneumatic compression and deep vein thrombosis prevention. A meta-analysis in postoperative patients.
Urbankova J, Quiroz R, Kucher N, Goldhaber SZ.
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Our objective was to overview the effectiveness of intermittent pneumatic compression (IPC) devices to prevent deep vein thrombosis (DVT) in postoperative patients, using meta-analysis methodology. We searched the Medline, metaRegister of Controlled Trials, and Cochrane database for studies published between 1970 and October 2004. Our inclusion criteria were: 1) randomized controlled trial of IPC versus no prophylaxis, 2) at least 20 patients per group, 3) at least one diagnostic DVT imaging test in all patients, and 4) clinical follow-up for at least the duration of hospitalization. A total of 2,270 patients were included in 15 eligible studies: 1,125 and 1,145 in the IPC and no prophylaxis group, respectively. The included studies formed a total of 16 treatment groups and were conducted in orthopedic (5), general surgical (4),oncologic (3), neurosurgical (3) and urologic (1) patient populations. In comparison to no prophylaxis, IPC devices reduced the risk of DVT by 60% (relative risk 0.40, 95% CI 0.29 - 0.56; p < 0.001). Contemporary randomized trials should be undertaken to test the utility of IPC in hospitalized medical patients as well as combined pharmacological plus IPC prophylaxis in both medical and surgical patients.

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Hamostaseologie. 2005 Nov;25(4):356-66.
[Diagnosis and treatment of venous thrombosis]
[Article in German]
Hach-Wunderle V.
Krankenhaus Nordwest--Gefasszentrum, Steinbacher Hohl 2-26, 60488 Frankfurt am Main. Hach-Wunderle@t-online.de

In the diagnosis of deep vein thrombosis in ambulatory patients, the recommended initial steps are assessment of clinical probability (CP) and a sensitive D-dimer test. With a low CP and negative D-dimer, thrombosis can be ruled out. All other constellations require further investigation with imaging techniques. Compression ultrasonography is the first-line investigation. Low-molecular weight heparin is the treatment of choice for uncomplicated venous thrombosis. Secondary prophylaxis with a vitamin K antagonist is introduced in parallel as quickly as possible. The duration of treatment depends on the exposure and predisposing factors, weighing carefully the risk of recurrence on the one hand against the risk of bleeding on the other. If there are contraindications to anticoagulation with heparins or coumarins, various other anticoagulant drugs are available.

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MMW Fortschr Med. 2005 Nov 24;147(47):40-2, 44-6.
[Treatment options in deep vein thrombosis]
[Article in German]
Bauersachs RM.
Medizinische Klinik IV Max-Ratschow-Klinik fur Angiologie Stadtisches Klinikum Darmstadt. Rupert.Bauersachs@Klinikum-Darmstadt.de

In the event of a deep vein thrombosis, the major concern is to prevent the subsequent development of an embolism or a recurrence. The therapeutic time gap to the development of the full effect of the vitamin K antagonists is bridged in the initial acute treatment phase with low molecular weight heparin (LMWH) or fondaparinux. In patients in whom vitamin K antagonists are contraindicated, or in pregnancy, secondary prophylaxis is alternatively continued with dose-adjusted LMWH. Compression therapy serves merely to prevent a post-thrombotic syndrome.

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Surg Neurol. 2005 Oct;64(4):295-301.
A review of the risks and benefits of differing prophylaxis regimens for the treatment of deep venous thrombosis and pulmonary embolism in neurosurgery.
Epstein NE.
Department of Neurosurgery, The Albert Einstein College of Medicine, Bronx, NY 10461; Division of Neurosurgery, Department of Surgery, Winthrop University Hospital, Mineola, NY 11501.

BACKGROUND: Annually, 2 million people in the United States develop deep venous thrombosis (DVT), and nearly 100000 sustain fatal pulmonary emboli. Prophylaxis against DVT/pulmonary embolism (PE) is a critical issue, and options include elastic stockings, intermittent pneumatic compression stockings, low-dose unfractionated heparin (5000 U every 8-12 hours), and low molecular-weight heparin (ie, enoxaparin and dalteparin). The risks and benefits associated with different prophylaxis regimens used in the prevention of DVT and PE in neurosurgical procedures were analyzed. METHODS: Neurosurgical studies focusing on different methods of prophylaxis used for the prevention of DVT and PE were reviewed. The efficacy, risks, and benefits of varied treatment options were evaluated, with particular emphasis on minor and major hemorrhages occurring where heparin-based protocols were used. RESULTS: In Flinn et al series (Arch Surg. 1996;131(5):472-80), the incidence of DVT was greater for cranial (7.7%) than spinal procedures (1.5%). Although intermittent pneumatic compression devices provided adequate reduction of DVT/PE in some cranial and combined cranial/spinal series, low-dose subcutaneous unfractionated heparin or low molecular-weight heparins further reduced the incidence, not always of DVT, but of PE (Br J Neurosurg 1995;9(2):159-63; J Intensive Care Med 2003;18(2):59-79). Nevertheless, low-dose heparin-based prophylaxis in cranial and spinal series risks minor and major postoperative hemorrhages: 2% to 4% in a cranial series, 3.4% minor and 3.4% major hemorrhages in a combined cranial/spinal series, and a 0.7% incidence of major/minor hemorrhages in a spinal series (J Neurosurg 2003;99(4):680-4; Neurosurgery 1986;18(4):440-5; Eur Spine J 2004;13(1):1-8; J Intensive Care Med 2003;18(2):59-79). CONCLUSIONS: Although mechanical prophylaxis provided effective prophylaxis against DVT/PE in many series, the added efficacy of low-dose heparin regimens has to be weighed against risks of major postoperative hemorrhages and their neurological sequelae.

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Br J Surg. 2005 Oct;92(10):1212-20.
Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery.
Agnelli G, Bergqvist D, Cohen AT, Gallus AS, Gent M.
Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.

BACKGROUND:: The aim of this study was to assess whether the synthetic factor Xa inhibitor fondaparinux reduced the risk of venous thromboembolism more efficiently than the low molecular weight heparin dalteparin in patients undergoing major abdominal surgery. METHODS:: In a double-blind double-dummy randomized study, patients scheduled for major abdominal surgery under general anaesthesia received once-daily subcutaneous injections of fondaparinux 2.5 mg or dalteparin 5000 units for 5-9 days. Fondaparinux was started 6 h after surgery. The first two doses of dalteparin, 2500 units each, were given 2 h before surgery and 12 h after the preoperative administration. The primary outcome measure was a composite of deep vein thrombosis detected by bilateral venography and symptomatic, confirmed deep vein thrombosis or pulmonary embolism up until day 10. The main safety outcome measure was major bleeding during treatment. RESULTS:: Among 2048 patients evaluable for efficacy, the rate of venous thromboembolism was 4.6 per cent (47 of 1027) with fondaparinux compared with 6.1 per cent (62 of 1021) with dalteparin, a relative risk reduction of 24.6 (95 per cent confidence interval -9.0 to 47.9) per cent (P = 0.144), which met the predetermined criterion for non-inferiority of fondaparinux. Major bleeding was observed in 49 (3.4 per cent) of 1433 patients given fondaparinux and 34 (2.4 per cent) of 1425 given dalteparin (P = 0.122). CONCLUSION:: Postoperative fondaparinux was at least as effective as perioperative dalteparin in patients undergoing high-risk abdominal surgery. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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Neurology. 2005 Sep 27;65(6):865-9.
Prevention of venous thrombosis in patients with acute intracerebral hemorrhage.
Lacut K, Bressollette L, Le Gal G, Etienne E, De Tinteniac A, Renault A, Rouhart F, Besson G, Garcia JF, Mottier D, Oger E; VICTORIAh (Venous Intermittent Compression and Thrombosis Occurrence Related to Intra-cerebral Acute hemorrhage) Investigators.
Groupe d'Etude de la Thrombose de Bretagne Occidentale, Equipe d'Accueil 3878, Cavale Blanche Hospital, Brest, France. karine.lacut@chu-brest.fr

OBJECTIVE: To assess intermittent pneumatic compression (IPC) in the prevention of venous thromboembolism (VTE). METHODS: The authors randomly allocated patients with a documented intracerebral hemorrhage (ICH) to elastic stockings (ES) alone or combined with IPC. The primary outcome was a combined criteria assessed at day 10: a symptomatic and well-documented VTE, or a death arising before day 10 and related to pulmonary embolism (PE), or an asymptomatic deep vein thrombosis (DVT) of the lower limbs detected by compression ultrasonography (CUS). Outcome assessment was blinded. RESULTS: One hundred fifty-one patients were randomized; 133 (88%) patients were evaluated at day 10. No clinical suspicion of VTE arose before day 10. Fourteen patients died before having a CUS but no death was definitely related to PE. Fourteen asymptomatic DVT were detected by CUS: three (4.7%) in the ES + IPC group (all distal) and 11 (15.9%) in the ES group (three proximal and eight distal). ES combined with IPC is associated with a reduced risk of asymptomatic DVT compared to ES alone: relative risk, 0.29 (95% CI 0.08 to 1.00). CONCLUSIONS: Asymptomatic deep vein thrombosis (DVT) was detected at day 10 in 15.9% of patients wearing elastic stockings alone. Intermittent pneumatic compression significantly decreased the occurrence of asymptomatic DVT for patients with intracerebral hemorrhage.

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Eur J Vasc Endovasc Surg. 2005 Sep 15; [Epub ahead of print]
Pulse-spray Pharmacomechanical Thrombolysis for Proximal Deep Vein Thrombosis.
Yamada N, Ishikura K, Ota S, Tsuji A, Nakamura M, Ito M, Isaka N, Nakano T.
First Department (Cardiovascular Division) of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan.

OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and feasibility of pulse-spray pharmacomechanical thrombolysis to treat proximal deep vein thrombosis (DVT) in conjunction with the placement of a non-permanent IVC filter. METHODS: We studied 31 consecutive patients with acute proximal DVT defined as the inferior vena cava (IVC), iliac vein and/or femoral vein, who were diagnosed using duplex ultrasonography and/or contrast venography. All were treated with pulse-spray urokinase. Early success was assessed by comparing the pre- and post-treatment venographic severity score. Non-permanent IVC filters were used to reduce the risk of pulmonary thromboembolism. RESULTS: The average total urokinase dose was 1.71 million IU (range: 0.72-3.6 million IU) and the average duration of therapy was 2.4 days. The average percentage of thrombus lysed was 85% (range: 22-100%). A large thrombus trapped by the filter was detected using cavography before extraction of the filter in one patient. There was no major treatment-related adverse event. CONCLUSION: The combination of pulse-spray pharmacomechanical thrombolysis and the prophylactic use of a non-permanent IVC filter was a safe and effective approach for treating acute proximal DVT.

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Semin Vasc Surg. 2005 Sep;18(3):166-75.
Vena cava filters: uses and abuses.
Rectenwald JE.
Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.

Currently, there are more than 10 permanent and optional retrievable vena cava filters in use in North America and Europe. Indications for inferior vena cava (IVC) filter placement are intuitive and filters are used in patients who have deep venous thrombosis (DVT) and contraindications to anticoagulation, or in patients who hemorrhage while anticoagulated for DVT. Multiple studies have proposed broadening the use of IVC filters as primary venous thromboembolism (VTE) prophylaxis in certain patient populations. Many permanent IVC filters have been well studied and have superior performance characteristics. On the other hand, optional retrievable IVC filters are attractive in the patient with a well-defined, short-term risk for VTE and contraindications to anticoagulation. Filter retrieval after the patient can be anticoagulated would eliminate the long-term risk of DVT associated with permanent IVC filter placement. Unfortunately, most optional retrievable filters are relatively new and have little to no data on their long-term performance when used as permanent filters, and the percentage of retrievable filters actually removed is less than 50%. The spirited debate concerning which patient should get which filter is just beginning. More prospective, randomized trials evaluating optional retrievable filters are needed to answer these important questions.

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Semin Vasc Surg. 2005 Sep;18(3):158-65.
Prophylactic indications for vena cava filters: critical appraisal.
Rutherford RB.
Emeritus Professor of Surgery, Department of Surgery, University of Colorado Medical School, Denver, CO.

Vena caval filters (VCFs) were developed and initially used for therapeutic indications, primarily to prevent recurrence of pulmonary embolism (PE) or its occurrence in selected cases of deep venous thrombosis (DVT), where risk of PE was very high and anticoagulant therapy (AC Rx) was deemed ineffective, contraindicated by concurrent disease, or had to be discontinued because of complications. Prophylactic indications-where there was no DVT or PE but the risk of them was considered very high and AC Rx was contraindicated or considered ineffective-were invoked relatively infrequently at first, but when percutaneous placement became routine in the late 1980s, this indication increased steadily. The categories of patients considered at high-enough risk of venous thromboembolism (VTE), albeit temporary, to justify VCF have also expanded steadily, most with little objective basis for choosing VCFs over other methods of prophylaxis. In many of these prophylactic categories, eg, patients undergoing surgery associated with a high risk of VTE, the risk is for a limited period only, until the patient is ambulatory or AC Rx can be instituted. In addition, there are potential disadvantages to leaving a permanent filter in, especially in younger patients with an extended longevity outlook and no ongoing risk of VTE. This was brought out in the PREPIC trial. This realization has, in turn, spurred interest in developing temporary or retrievable filters for short-term prophylactic use. No design has yet proven entirely satisfactory for this purpose, but the practice of placing such filters for prophylactic indications has steadily grown, using available devices. This article critically reviews these trends, suggests directions for future developments, and recommends necessary studies on which to base the practice of prophylactic VCF use.

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Semin Vasc Surg. 2005 Sep;18(3):153-7.
A unified approach to axillosubclavian venous thrombosis in a single hospital admission.
Caparrelli DJ, Freischlag J.
Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD.

Spontaneous or effort-related thrombosis of the axillosubclavian vein, termed Paget-Schroetter syndrome, is thought to be related to repetitive upper extremity physical activity, most commonly afflicting young, otherwise healthy, individuals. For the past 25 years, the mainstay of treatment for acute axillosubclavian venous thrombosis has consisted of early local catheter-directed thrombolytic therapy, an interval period of anticoagulation (3 months), and late surgical decompression of the thoracic outlet, with either a transaxillary or supraclavicular first rib resection. Immediate thrombolytic therapy followed by early surgical decompression has also been suggested previously, but has only recently been shown to be safe and efficacious, while significantly decreasing the duration of disability suffered by patients with this form of thoracic outlet syndrome. Therefore, a unified approach to acute axillosubclavian venous thrombosis in a single hospital admission should be considered an alternative standard of care for treatment of Paget-Schroetter syndrome.

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Semin Vasc Surg. 2005 Sep;18(3):148-52.
Ambulation and compression after deep vein thrombosis: dispelling myths.
Partsch H.
Medical University Vienna, Austria.

The traditional dogma of putting mobile patients with acute deep vein thrombosis into bed for several days has been challenged by some studies that showed a better clinical outcome with walking exercises under good compression. Repeated lung scans did not show an increased risk of new pulmonary embolism. There was a faster and more intense reduction of pain and swelling and a clear quality-of-life benefit. Immediate ambulation with compression reduces the propagation of thrombi and has a positive impact regarding development of postthrombotic syndrome. Patients selected for home therapy should not only be instructed how to inject their low-molecular-weight heparin but should also be educated to walk around with good compression. Until now the important principle of avoiding the venous stasis associated with bed rest has found broad acceptance in the field of primary prevention of venous thromboembolism. Modern antithrombotic management of patients with acute venous thrombosis should include early ambulation in conjunction with appropriate compression therapy.

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Int Angiol. 2005 Sep;24(3):255-7.
Are we managing primary upper limb deep venous thrombosis aggressively enough in the district?
Fassiadis N, Roidl M, South M.
Department of Vascular Surgery, Maidstone Hospital, Kent, UK.

AIM: The objective of this retrospective study was to analyse risk factors, management and outcome of primary upper limb deep venous thrombosis (ULDVT, Paget von Schroetter syndrome) in 4 district hospitals. METHODS: The study group audited between May 1995 and January 2004 comprised of 24 patients with primary ULDVTs (8 male, 16 female; age range 21-80 years, mean 46 years). RESULTS: Common risk factors included smoking (n=8, 33.3%) and hormonal therapy for women (n=4, 25%). Diagnosis was established by duplex ultrasound alone in 13 patients (54.2%), by venogram alone in 9 patients (37.5%) and by both investigations in 2 patients (8.3%). A thrombophilia screen was performed in 19 patients (79.2%) of which 5 patients (20.8%) were identified with a hypercoagulable state. Twenty-three patients were anticoagulated (95.8%). One patient (4.2%) was initially thrombolysed and subsequently anticoagulated. Overall symptoms resolved or improved in 14 patients (58.3%), symptoms persisted in 8 patients (33.3%) and in 2 patients (8.3%) the outcome was not documented. Only one patient was further evaluated and identified as having thoracic outlet compression. Most patients were managed by physicians (n=19 versus surgeons n=5). CONCLUSIONS: This study reveals that most patients with primary ULDVT are treated with anticoagulation alone probably based on protocols for lower limb deep vein thromboses which results in an unacceptable high number of patients (33.3%) with persisting disability. Therefore, we suggest a more proactive approach in such patients with evaluation for thoracic outlet compression.

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J Bone Joint Surg Am. 2005 Sep;87(9):2097-112.
Prevention of venous thromboembolic disease after total hip and knee arthroplasty.
Lieberman JR, Hsu WK.
Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California at Los Angeles, Center for Health Sciences 76-134, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA. jlieberman@mednet.ucla.edu

Patients undergoing total hip and knee arthroplasty are at increased risk for the development of venous thromboembolic disease, and there is general agreement that these patients require prophylaxis. The selection of a prophylactic agent involves a balance between efficacy and safety and often needs to be individualized for specific patients and institutions. Despite extensive research, the ideal agent for prophylaxis against deep venous thrombosis has not been identified. The results of randomized trials indicate that low-molecular-weight heparin, warfarin, and fondaparinux are the most effective prophylactic agents after total hip arthroplasty and that low-molecular-weight heparin, warfarin, fondaparinux, and pneumatic compression boots are the most effective agents after total knee arthroplasty. The duration of prophylaxis against deep venous thrombosis after total hip and knee arthroplasty remains controversial. Prophylaxis should be continued beyond hospital discharge. In the future, the determination of the duration of prophylaxis will be based on the risk stratification of individual patients. The practice of discharging patients from the hospital without prophylaxis, even when the decision is based on negative results of procedures that screen for the presence of deep venous thrombosis, is not cost-effective.

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Blood Rev. 2005 Sep;19(5):235-41. Epub 2005 Mar 24.
Travel and thrombosis.
Watson HG.
Department of Haematology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, Scotland, UK. henry.watson@arh.grampian.scot.nhs.uk

The available evidence suggests an association between long distance travel and the development of venous thromboembolism. The main problem for travellers and physicians is the interpretation of the evidence and its translation into appropriate advice on the risk and the prevention of thrombosis. Most available data relate to air travel. Thrombosis risk is greater following journeys of more than 8 h and those at greatest risk are travellers with a history of venous thromboembolism or risk factors. Based on the best evidence available the risk of symptomatic venous thromboembolism after flights of more than 12 h is 0.5%. It is likely that stasis plays a major role in the aetiology of travel related thrombosis. The evidence for hypobaric hypoxia induced coagulation activation requires confirmation. There is evidence that compression stockings and low molecular weight heparin prevent asymptomatic deep vein thrombosis (DVT) but clinical DVT has been observed in long distance flyers in spite of prophylaxis with aspirin and stockings.

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Ann Pharmacother. 2005 Jul;39(7):1182-1187. Epub 2005 Jun 14.
Tinzaparin in Outpatients with Pulmonary Embolism or Deep Vein Thrombosis.
Dager WE, King JH, Branch JM, Chow SL, Ferrer RE, Pak S, Togioka PY, White RH.
Department of Pharmaceutical Services, University of California (UC) Davis Medical Center, Sacramento, CA; Clinical Professor of Pharmacy, School of Pharmacy, University of California at San Francisco (UCSF); Associate Clinical Professor of Medicine, UC Davis School of Medicine.

BACKGROUND: The low-molecular-weight heparins (LMWHs) have been shown to be effective in the outpatient treatment of deep vein thrombosis (DVT). Data regarding outpatient use of any LMWH in pulmonary embolism (PE) or tinzaparin in DVT while transitioning therapy to a vitamin K antagonist are limited. OBJECTIVE: To determine the safety and efficacy of tinzaparin in patients with either DVT or PE being transitioned to warfarin during LMWH therapy in the outpatient setting. METHODS: All patients who were treated with at least one outpatient dose of tinzaparin for venous thromboembolism (VTE) were identified. Charts of all patients followed within the University of California Davis healthcare system were reviewed. The incidence of bleeding and recurrent thromboembolism over a minimum of the first 4 weeks to a maximum of 12 weeks after initiating anticoagulation was assessed. RESULTS: A total of 178 patients with acute VTE were treated with tinzaparin, and outcomes could be determined in 140 cases. Forty-seven percent of these patients had objectively documented PE. Only one (0.7%) case of recurrent VTE was observed. Major bleeding was documented in 5 (3.6%) and minor bleeding in 8 (5.8%) patients. Two bleeding events, both major, occurred during tinzaparin therapy. CONCLUSIONS: Outpatient use of tinzaparin during transition to warfarin therapy in the treatment of VTE, including PE, appears to be feasible in patients who are judged candidates for home therapy.

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Am J Obstet Gynecol. 2005 Jul;193(1):216-9.
Thrombosis during pregnancy and the postpartum period.
James AH, Tapson VF, Goldhaber SZ.

Objective To describe the circumstances surrounding deep vein thrombosis among pregnant or postpartum patients enrolled in a large multicenter registry. Study design Consecutive patients with ultrasound-confirmed deep vein thrombosis were enrolled at 183 institutions during a 6-month period from October 2001 to March 2002. Fifty-three who were either pregnant or within 6 weeks postpartum were analyzed. Results Thirty-four were pregnant and 19 were postpartum. Among those pregnant, 44% experienced deep vein thrombosis in the first trimester, 24% in the second, and 26% in the third. Deep vein thrombosis occurred in the left lower extremity in 76% of the pregnant and 47% of the postpartum women. Four pregnant and 2 postpartum women had pelvic vein thrombosis. Among those postpartum, 74% had undergone surgery within 3 months. Conclusion During pregnancy, the risk of deep vein thrombosis begins in the first trimester. Thus, we believe that when prophylaxis is indicated, it should be initiated early in gestation.

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Expert Opin Drug Saf. 2005 Jul;4(4):707-21.
The safety of fondaparinux for the prevention and treatment of venous thromboembolism.
Turpie AG.
General Division, Hamilton Health Sciences Corporation, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada. turpiea@mcmaster.ca

Fondaparinux is the first synthetic selective Factor Xa inhibitor. Along with its antithrombotic efficacy, the safety of fondaparinux has been documented in several Phase II and III clinical trials, including the prevention of venous thromboembolism in patients undergoing major orthopaedic surgery or high-risk abdominal surgery, or in acutely ill medical patients with restricted mobility, and the treatment of patients with deep-vein thrombosis and pulmonary embolism. In all these indications, the safety of fondaparinux used according to its registered regimen was similar to that of reference comparators. In conclusion, due to its superior efficacy and satisfactory safety, fondaparinux may substantially improve the prevention and treatment of venous thrombosis.

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Circulation. 2005 Jul 19;112(3):416-22. Epub 2005 Jul 11.
Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study.
PREPIC Study Group.

BACKGROUND: In a randomized trial in patients with proximal deep-vein thrombosis, permanent vena cava filters reduced the incidence of pulmonary embolism but increased that of deep-vein thrombosis at 2 years. An 8-year follow-up was performed to assess their very long-term effect. METHODS AND RESULTS: Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and postthrombotic syndrome were obtained once a year for up to 8 years. All documented events were reviewed blindly by an independent committee. Outcome data were available in 396 patients (99%). Symptomatic pulmonary embolism occurred in 9 patients in the filter group (cumulative rate 6.2%) and 24 patients (15.1%) in the no-filter group (P=0.008). Deep-vein thrombosis occurred in 57 patients (35.7%) in the filter group and 41 (27.5%) in the no-filter group (P=0.042). Postthrombotic syndrome was observed in 109 (70.3%) and 107 (69.7%) patients in the filter and no-filter groups, respectively. At 8 years, 201 (50.3%) patients had died (103 and 98 patients in the filter and no-filter groups, respectively). CONCLUSIONS: At 8 years, vena cava filters reduced the risk of pulmonary embolism but increased that of deep-vein thrombosis and had no effect on survival. Although their use may be beneficial in patients at high risk of pulmonary embolism, systematic use in the general population with venous thromboembolism is not recommended.

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Aust Fam Physician. 2005 Jul;34(7):555-61.
Pulmonary embolism. Assessment and management.
Rees M, Williams TJ.
Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Victoria.

BACKGROUND: Pulmonary embolism (PE) is a potentially life threatening disorder most commonly seen in debilitated patients with other common medical problems. OBJECTIVE: This article aims to increase the reader's understanding of the aetiology and pathophysiology of PE so as to identify particular at risk patients. An approach to investigation and management will also be explored. DISCUSSION: Pulmonary embolism has an incidence of approximately two per 1000 per year, generally as a consequence of deep venous thrombosis (DVT), in the setting of immobility. Deep venous thrombosis and PE during a prolonged airline flight in an otherwise fit person is a rare event. Clinical assessment and simple investigations form the basis of initial evaluation. The confirmatory test is generally a ventilation/perfusion lung scan or a computerised tomography pulmonary angiogram. There is still considerable discussion as to which is the better test - both are valid if performed to acceptable standards - thus local factors often determine which is performed. Further tests may be needed in those with intermediate probability of PE after a confirmatory test. These patients, and those presenting with massive PE, may require pulmonary angiography (still regarded as the gold standard test). Treatment is anticoagulation, typically with low molecular weight heparin followed by 6 months of warfarin. Thrombolytic therapy is reserved for the acute massive presentation. Appropriate treatment reduces mortality substantially, however, rarely the clot remains unresolved and thromboembolic pulmonary hypertension (requiring expert evaluation) develops.

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Clin Orthop Relat Res. 2005 Jul;(436):138-143.
Thromboembolic Disease Prophylaxis in Total Hip Arthroplasty.
Sarmiento A, Goswami A.
>From the *University of Miami Medical School, Miami, FL; and daggerHope Hospital, Salford, Manchester, UK.

We sought to determine if using aspirin and exercise as prophylaxis against thromboembolic disease in patients having total hip arthroplasties would provide results as effective as or better than those reported in the literature using other chemical agents. One thousand eight hundred thirty-five total hip arthroplasties were done in 1585 patients using a posterior approach. Surgery was done with the patient under general anesthesia in 459 instances and regional anesthesia in 1376 instances. Graduated elastic stockings were used in 1117 instances and intermittent compression stockings were used in 718 instances. Passive exercises of the major joints of the operated extremity were done intraoperatively, and active exercises were done postoperatively. Patients received a suppository containing 10 grains of aspirin immediately after surgery and 325 mg twice a day for the length of their hospitalization. Fatal pulmonary embolism developed after two (0.10%) surgical procedures. Nonfatal pulmonary embolisms were diagnosed in 17 (0.9%) patients, and deep venous thrombosis was diagnosed in 17 (0.9%) patients. The low incidence of thromboembolic complications recorded in this series suggests that our postoperative protocol, including 325 mg of aspirin twice a day during hospitalization and exercise, is an effective and inexpensive method of prophylaxis after total hip arthroplasty.Level of Evidence: Therapeutic study, Level IV (case series-no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

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Zentralbl Chir. 2005 Jun;130(3):250-4.
[Vena cava filter -- is there an indication for implantation?]
[Article in German]
Burger T, Halloul Z, Tautenhahn J, Gebauer T, Lippert H.
Klinik fur Allgemein-, Viszeral- und Gefasschirurgie, Medizinische Fakultat, Otto-von-Guericke-Universitat, Magdeburg.

The indication of vena cava filter implantation is controversially discussed. On the basis of the available literature and our own results a critical analysis of this issue is given. Between 1994 and 2003, we inserted a total of 29 vena cava filters; 24 temporary and 5 permanent filters. In twelve patients, the placement of the filter was indicated due to pulmonary embolism and a contra-indication to dose adjusted heparin therapy. Seven additional patients experienced a recurrent pulmonary embolism despite adequate heparin therapy. An additional prophylactic filter insertion was carried out in ten patients. The temporary vena cava filters were left in place between 7 to 38 days with an average of 17 days. Total implantation time of temporary filters was scheduled until complete mobilisation of the patients, generally in conjunction with an effective dosage of oral anticoagulants. No patient died in connection with the insertion of the filter and no further pulmonary embolisms occurred. One case of inferior vena cava thrombosis occurred in each group of temporary and permanent filters. In one third of the removed filter systems, thrombi in the filter were found. Local infections of the catheter and introducer sets were observed in two patients. Moreover, in one case the strut of a temporary filter broke and subsequently dislocated 17 days after insertion. However, there is little evidence concerning vena cava filters, and further investigations are necessary. Until additional data are available, filters should generally be restricted to patients with deep venous thrombosis and pulmonary embolism who cannot receive anticoagulation, and highly selected cases.

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Curr Treat Options Cardiovasc Med. 2005 Jun;7(2):149-158.
Temporary Vena Caval Interruption and Thrombolysis in the Management of Deep Vein Thrombosis.
Elliott G, Stevens S.
Pulmonary Division, LDS Hospital,Eighth Avenue and C Street, Salt Lake City,UT 84143,USA. gelliot@ihc.com.

Temporary interruption of the inferior vena cava (IVC) with a retrievable filter should be considered in patients with objectively verified proximal deep vein thrombosis (DVT) of the legs who have a temporary contraindication to therapeutic anticoagulation, or in patients who experience severe complications from anticoagulation. The risk of the temporary filter being left in place permanently must be considered. Use of a retrievable filter in conjunction with therapeutic anticoagulation during the early phase of therapy for acute DVT in patients whose cardiopulmonary reserve is limited (ie, those with pre-existing pulmonary hypertension) may be a future indication for this intervention. Interruption of the superior vena cava with a retrievable filter has been performed in a small number of cases, but there are insufficient data to guide risk:benefit analysis for this procedure. Thrombolysis, either systemic or local, results in a higher rate of thrombus resolution than anticoagulation alone. However, the long-term benefit of thrombolysis in preventing or improving the post-thrombotic syndrome remains unproven. Due to the substantial risk and cost of thrombolytic therapy, it should not be performed in the routine treatment of DVT. Thrombolytic therapy, in the absence of contraindication, should be considered in highly symptomatic, massive iliofemoral DVT. Catheter-directed thrombolytic therapy has shown promise in case series, but its role remains to be elucidated in randomized trials.

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Minerva Chir. 2005 Apr;60(2):119-35.
16-year follow-up study of Vena Cava Filters Group.
Emanuelli G, Farina A, Segramora V, Pecora N.
Vascular Surgery Unit III, Galeazzi Orthopaedic Institute, Milan, italy.

AIM: The prevalence of venous thromboembolic disease (VTED) is between 0.05% and 0.1% whereas its incidence is approximately 0.1%. Out of 100 patients with deep vein thrombosis (DVT), 5 will develop clinically serious pulmonary embolism (PE), one of which will be fatal. It is well known from the literature that surgical interventions carried out without antithrombotic prophylaxis have a 30% incidence of DVT, which can be halved with adequate prophylaxis. The aim of this study is to evaluate the immediate, middle- and long-term complications of caval filters by identifying any of the problems connected with or independent of the presence of the filter, also in relation to international literature data. METHODS: In view of the evolution of VTED surgical prevention methods, we have analyzed our case record composed of 821 patients (October 1984-October 2002), treated with different surgical solutions for VTED, with indications for the placement of 634 caval filters. RESULTS: The 30-day follow-up of all the 634 filters placed (100%) shows no mortality from the procedure and any of its immediate complications. The middle-term follow-up (from 1 month to 5 years) of 361 filters (57%) shows 0.55% mortality from PE while the long-term follow-up (5-16 years) of 105 filters (17%) shows a percentage decrease in all complications and no mortality from PE. The results also show a progressive annual decrease in the number of filters placed. CONCLUSIONS: The lower incidence of complications, compared to that reported in the literature, can be attributed to both improved operator dexterity in the placement of the filter and correct management of the complications. The lower number of filters used can be explained by improved therapeutic possibilities with new low molecular weight heparins (LMWH) and by current diagnostic as well as instrumental and biochemical monitoring methodologies.

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J Orthop Trauma. 2005 Apr;19(4):234-240.
Thromboembolic Disease Prophylaxis in Patients With Hip Fracture: A Multimodal Approach.
Westrich GH, Rana AJ, Terry MA, Taveras NA, Kapoor K, Helfet DL.
>From the *Hospital for Special Surgery, New York, NY; daggerDepartment of Orthopaedic Surgery, Weill Medical College of Cornell University, New York, NY; and double daggerSUNY Downstate Medical School, Brooklyn, NY.

OBJECTIVES:: To assess if pneumatic compression in conjunction with chemoprophylaxis is an effective way to reduce the incidence of deep vein thrombosis in orthopedic trauma patients sustaining fragility hip fractures. DESIGN:: Two hundred patients admitted to the authors' institution between May 1998 and June 2002 for fractures of the hip were prospectively studied. All patients were treated operatively and received the VenaFlow(R) calf compression device on both lower extremities immediately following surgery. Chemical prophylaxis of either aspirin (n = 67) or warfarin (n = 133) was administered in addition to mechanical compression. A noninvasive serial color flow duplex scan was performed 1 to 11 days postoperatively (mean 4.5 days) to determine the presence or absence of deep vein thrombosis. All patients were followed clinically 3 months postoperatively for a clinical evaluation of symptomatic deep vein thrombosis or pulmonary embolism. RESULTS:: Overall, the incidence of deep vein thrombosis was 3.5% (7 of 200) and included only 1 proximal thrombosis (1 out of 200, or 0.5%) and no pulmonary embolism. Five of the 7 patients positive for deep vein thrombosis were in the mechanical compression and warfarin prophylaxis group and 2 were in the aspirin arm of the study. For patients with deep vein thrombosis, the average number of risk factors was 3.71, whereas patients without clots averaged 1.75 clinical risk factors (P </= 0.05). Three patients in the warfarin group developed bleeding complications (1 with a gastrointestinal bleed and 2 with minor bleeding not at the operative site). No evidence of a symptomatic deep vein thrombosis or pulmonary embolism was reported within a 3-month period following hospitalization. CONCLUSIONS:: Our findings suggest mechanical compression with the VenaFlow(R) calf compression device in conjunction with chemoprophylaxis is an effective means of reducing thromboembolic disease in this high-risk population.

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Lancet. 2005 Apr;365(9465):1163-74.
Deep vein thrombosis.
Kyrle PA, Eichinger S.
Medical University of Vienna, Department of Internal Medicine I, Wahringer Gurtel 18-20, 1090 Vienna, Austria. paul.kyrle@meduniwien.ac.at

Deep vein thrombosis and its sequelae pulmonary embolism and post-thrombotic syndrome are some of the most common disorders. A thrombus either arises spontaneously or is caused by clinical conditions including surgery, trauma, or prolonged bed rest. In these instances, prophylaxis with low-dose anticoagulation is effective. Diagnosis of deep vein thrombosis relies on imaging techniques such as ultrasonography or venography. Only about 25% of symptomatic patients have a thrombus. Thus, clinical risk assessment and D-dimer measurement are used to rule out deep vein thrombosis. Thrombus progression and embolisation can be prevented by low-molecular-weight heparin followed by vitamin K antagonists. Use of these antagonists for 3-6 months is sufficient for many patients. Those with antithrombin deficiency, the lupus anticoagulant, homozygous or combined defects, or with previous deep vein thrombosis can benefit from indefinite anticoagulation. In cancer patients, low-molecular-weight heparin is more effective than and is at least as safe as vitamin K antagonists. Women seem to have a lower thrombosis risk than men, but pregnancy or use of oral contraceptives or hormone replacement therapy represent important risk factors.

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Nippon Geka Gakkai Zasshi. 2005 Mar;106(3):227-31.
[Pathogenesis, diagnosis, and treatment of postoperative deep vein thrombosis]
[Article in Japanese]
Ohgi S, Kanaoka Y, Ito N, Suzuki Y, Taniguchi Y.
Division of Organ Regeneration Surgery, Department of Surgery, Tottori University, Faculty of Medicine, Yonago, Japan.

Most postoperative deep vein thrombosis (DVT) arises from the venous systems of the pelvis and lower extremities, especially the soleal veins. Embolization of venous thrombi is related to the size and location of thrombi and movement of the lower limbs and commonly occurs within 1 week from the onset of formation. There are three steps in the final diagnosis of DVT: probable diagnosis by anamnesis and physical examination; screening diagnosis using quantitative tests; and definitive diagnosis using imaging tests. To determine embolic sources, venous echography, which is noninvasive and convenient, is the first choice. Therapeutic methods are selected based on thrombi extent and time after formation. Anticoagulant therapy is indicated in all cases except in patients with possible bleeding tendency and continues for 3 months or more. Among the endovascular therapies, catheter-directed thrombolysis is a more effective approach when combined with a temporary vena cava filter than operative thrombectomy. Although the prevention of DVT is mandatory for surgeons, it is difficult to avoid venous thromboembolism completely. Systemic early diagnosis and emergent therapeutic strategies for venous thromboembolism are clinically effective and promising.

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Nippon Geka Gakkai Zasshi. 2005 Mar;106(3):232-6.
[Postoperative venous thrombosis in general surgery patients and perioperative prophylaxis]
[Article in Japanese]
Horie H, Endo N, Sata N, Yasuda Y, Nagai H.
Department of Surgery, Jichi Medical School, Tochigi, Japan.

In a population of general surgery patients in Western countries, there was a 19% incidence of deep vein thrombosis (DVT) and a 1.6% incidence of pulmonary embolism (PE), with 0.9% of patients experiencing fatal PE. In Japan, there was a 15.8% incidence of DVT and a 0.34% incidence of PE, with 0.08% of patients experiencing fatal PE in a population of abdominal surgery patients. The incidences of PE and fatal PE in our department were 0.11% and 0.03%, respectively. We started to use intermittent pneumatic compression (IPC) for the prophylaxis of postoperative PE in 1999 and then added elastic stockings in 2002 and low-dose unfractionated heparin (LDUH) in 2003 for prophylaxis. The incidence of PE has dropped and that of fatal PE has become 0% with the use of such prophylactic measures. When the risk of venous thromboembolism of the 15 patients who experienced PE in our department were assessed using the Japanese Guidelines for Prevention of Venous Thromboembolism, 13 patients were assessed as high risk and 2 as low risk. The mean age and mean body mass index of the 15 patients were 54 yeas old and 24.8, respectively, and PE was not limited to obese or elderly patients. Such findings appear to indicate the difficulty of risk assessment for PE. Therefore we started to use IPC, elastic stockings, and LDUH for the prophylaxis of PE and DVT for all general surgery patients from April 2004. These prophylactic measures are recommended for the highest-risk patients in the Japanese Guidelines for Prevention of Venous Thromboembolism. There have so far been no serious bleeding complications with the administration of LDUH. We will continue to observe the effects of prophylaxis and the risk of bleeding.

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Drug Saf. 2005;28(4):333-349.
Safety Profile of Different Low-Molecular Weight Heparins Used at Therapeutic Dose.
Gouin-Thibault I, Pautas E, Siguret V.
Laboratoire d'Hematologie, Hopital Charles Foix (University Hospital of Paris), Ivry/Seine, France.

Low-molecular weight heparins (LMWHs) have been shown to be as safe and effective as unfractionated heparin (UFH) for the treatment of acute venous thrombosis and non-life-threatening pulmonary embolism. Different reports have shown that LMWHs may also be used to treat patients with unstable angina or non-Q-wave infarction. The safety of LMWHs used at therapeutic dose has been widely studied in pivotal clinical trials and analysed in several meta-analyses. However, despite the wide development and use of LMWHs, several issues regarding the safety and optimal use of LMWHs remain unanswered.The main adverse effect of LMWHs is bleeding and it is uncertain whether a weight-adjusted dosage regimen without laboratory monitoring can be used in patients with a high risk of bleeding, such as patients with renal failure, elderly patients, obese patients or pregnant women. These patients are usually excluded from clinical trials and only a few studies, not sufficiently powered to estimate efficacy and safety, have been carried out in these special populations. Most of the available data comes from pharmacokinetic or population pharmacodynamic studies or clinical reports. Results in patients with renal impairment who are not undergoing haemodialysis suggest that a reduction in calculated creatinine clearance levels is associated with an increased risk of accumulation of anti-Xa activity, the extent of which differs depending on the individual LMWH and the extent to which the compound is cleared by the kidney. The limited data available regarding the use of therapeutic doses of LMWHs in obese patients suggest that there is no need to cap the dose at a maximal allowable dose. Long-term (3-month) treatment with LMWHs appears to be as effective and safe as oral anticoagulant therapy for the treatment of venous thromboembolism. It appears that each LMWH is a distinct compound with unique pharmacokinetic and pharmacodynamic profiles. Until more data are available regarding these special populations, periodic monitoring of anti-Xa activity levels may be recommended to detect accumulation and/or an overdose and minimise the bleeding risk.The non-haemorrhagic adverse effects of the LMWHs include heparin-induced thrombocytopenia (HIT) and osteoporosis. The incidence of HIT appears to be lower with LMWHs than with UFH; there is currently not enough data to compare the frequency of HIT between the various LMWHs. LMWHs also appear to carry a lower risk of causing osteoporosis than UFH.In conclusion, studies that include special population patients are required to make conclusive recommendations concerning the safety and monitoring of the different LMWHs.

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Expert Opin Emerg Drugs. 2005 Feb;10(1):87-94.
Emerging strategies for treatment of venous thromboembolism.
Prandoni P.
University of Padua, Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, Via Ospedale Civile 105, 35128, Padua, Italy. paoloprandoni@tin.it.

Although considerable progress has been made in the treatment of venous thromboembolism (VTE), many unanswered questions remain, which are awaiting proper solution. Furthermore, new opportunities are emerging, which have the potential to rapidly change the therapeutic scenario. Selected patients with deep-vein thrombosis can be effectively and safely treated at home with fixed-dose low-molecular-weight heparins. The long-term use of low-molecular-weight heparins is likely to be more effective than and as safe as oral anticoagulants for the secondary prevention of VTE in cancer patients with venous thrombosis. Recent publications have unexpectedly raised a renewed interest on the use of thrombolytic drugs in patients with pulmonary embolism, at least in those who present with heart ventricular dysfunction. The optimal long-term treatment of VTE is still undefined. Finally, new categories of drugs are emerging, which have the potential to replace conventional anticoagulants in the near future. They include anti-Xa inhibitors, such as pentasaccharide, and antithrombin inhibitors, such as ximelagatran.

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Wien Med Wochenschr. 2005 Jan;155(1-2):11-3.
[Compression therapy in the treatment of acute deep vein thrombosis]
[Article in German]
Fink AM.
Dermatologische Abteilung, Wilhelminenspital der Stadt Wien, Wien, Osterreich. astrid.fink@wienkav.at

Especially in Europe patients with acute deep vein thrombosis (DVT) of the leg are treated with compression therapy. A look at the literature, however, reveals that the exact mechanism of compression therapy in the treatment of acute deep vein thrombosis is not completely understood. Effects on fibrinolysis, resolution of pain and swelling as well as a fixation of the thrombus towards the vessel wall have been discussed. The literature indicates that compression stockings were mostly used in the treatment of DVT although there is some evidence that inelastic compression bandages have a greater impact on resolution of swelling and pain. Large randomised multicenter trials are still not available. Furthermore, evidence-based data providing an advantage of thigh-length compression therapy in the treatment of acute DVT are lacking. Studies have, however, shown that compression therapy is a safe therapy and can reduce the development of postthrombotic syndrome after acute DVT.

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Wien Med Wochenschr. 2005 Jan;155(1-2):7-10.
Treatment of venous thromboembolism.
Eichinger S.
Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria. sabine.eichinger@meduniwien.ac.at

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are two manifestations of the same disorder, venous thromboembolism, and low-molecular weight heparin is the treatment of choice for both DVT and PE. Alternatively, intravenous adjusted-dose unfractionated heparin can be used in hemodynamically unstable patients with massive PE. Secondary thromboprophylaxis with vitamin K-antagonists (VKA) should be started as soon as the diagnosis is confirmed. The dose of VKA should be adjusted to a target international normalized ratio (INR) of 2.5. For most patients with PE, thrombolysis is not recommended. Vena cava filters should be restricted to patients with active bleeding or risk of serious bleeding, and to those in whom PE has recurred despite adequate anticoagulation. Several new antithrombotics with potential advantages over heparin and VKA have been evaluated in phase II and III trials, but are currently not licensed for the treatment of venous thromboembolic events.

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Int Angiol. 2004 Dec;23(4):305-16.
Outpatient treatment of venous thromboembolism using low molecular weight heparins. An overview.
Matsagas MI.
Vascular Surgery Unit, Department of Surgery, School of Medicine, University of Ioannina, Ioannina, Greece.

The development of low-molecular-weight heparins (LMWHs) was a significant advance in the treatment of venous thromboembolism (VTE). Their better bioavailability and more predictable anticoagulant activity than unfractionated heparin (UFH) allow subcutaneous administration without close laboratory monitoring, and thus make outpatient treatment of deep vein thrombosis (DVT) feasible. The safety and efficacy of outpatient treatment in selected patients were established in randomized clinical trials comparing subcutaneous LMWH administered primarily at home with inpatient intravenous UFH. Furthermore, during the last few years a large number of studies have supported these findings in various clinical settings of every-day practice. It is also important that home treatment has lead to substantial cost reductions along with improvement in patients' satisfaction and quality of life. Thus, outpatient treatment of DVT provides an opportunity, rarely seen in medicine, to improve patient care while reducing the overall VTE health-care cost, and it is likely that will be the preferred regime for the majority of patients in the future. However, the implementation of a home treatment program is not simple, as the risks of insufficient or excessive anticoagulation would be considerable. A structured protocol is necessary to ensure that patient care is optimal, and the keys to a successful outpatient treatment program are patient selection, patient education, patient access to health care team, appropriate follow-up and health care team communication.

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Curr Opin Crit Care. 2004 Dec;10(6):539-48.
Venous thromboembolism after trauma.
Knudson MM, Ikossi DG.
Department of Surgery, University of California, San Francisco, California 94110, USA. pknudson@sfghsurg.ucsf.edu

PURPOSE OF REVIEW: The trauma population is at increased risk of venous thromboembolic disease, a potentially preventable cause of mortality and morbidity. Although the association between trauma and venous thromboembolism has been recognized for more than a century, there is still great variability in the clinical practices with respect to prophylaxis. This thorough review of recent literature aims to clarify the incidence and risk factors for deep venous thrombosis and pulmonary embolism after trauma, review options and recommendations for detection of deep venous thrombosis and pulmonary embolism, and give evidence-based recommendations for prophylaxis. Special attention is paid to patients with spinal cord injury, patients with head injury, and pediatric trauma patients. RECENT FINDINGS: Highlights in this field during the past year include stratification of venous thromboembolism risk factors after trauma using a large national database, the expanded use of venous duplex ultrasound surveillance in the ICU and during rehabilitation, and investigations into the safety of low molecular weight heparins in patients with solid organ and traumatic brain injuries. Additionally, two new classes of anticoagulant drugs have been introduced for venous thromboembolism prophylaxis, and there are some preliminary studies on a temporary vena cava filter for the prevention of pulmonary embolism. SUMMARY: Venous thromboembolism remains an area of active clinical research focusing on evolving diagnostic techniques, newer methods of chemical and mechanical prophylaxis, and improved understanding of the etiologic factors of posttraumatic venous thromboembolism. These efforts will undoubtedly decrease the posttraumatic morbidity and mortality associated with venous thromboembolism.

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J Am Coll Surg. 2004 Dec;199(6):869-74.
Early experience with retrievable inferior vena cava filters in high-risk trauma patients.
Hoff WS, Hoey BA, Wainwright GA, Reed JF, Ball DS, Ringold M, Grossman MD.
Division of Traumatology, St Luke's Hospital, Bethlehem, PA 18015, USA.

BACKGROUND: This study describes the use of retrievable IVC filters in a select group of trauma patients at high risk for deep vein thrombosis (DVT) and pulmonary embolism (PE). STUDY DESIGN: Retrievable IVC filters were placed in selected trauma patients who met high-risk criteria for deep vein thrombosis and PE according to institutional clinical management guidelines. All filters were placed percutaneously in the interventional radiology suite. Indications for filter placement were based on injury complex, weight-bearing status, and contraindications to enoxaparin or pneumatic compression devices. IVC filters were either removed or maintained. RESULTS: Retrievable IVC filters were placed in 35 patients after blunt trauma. Twenty-six patients (74%) sustained at least one orthopaedic injury; 17 patients (49%) were diagnosed with a pelvis fracture. Activity was limited to bed rest or spinal precautions in 18 patients (51%). Enoxaparin was contraindicated in 32 patients (91%) and injuries precluded the use of pneumatic compression devices in 11 (31%). IVC filters were removed in 18 patients (51%), with no reported complications. Patients with orthopaedic injuries and pelvis fractures were less likely to have their filters maintained (p = 0.040). CONCLUSIONS: Retrievable IVC filters offer a versatile option for prophylaxis in trauma patients at high risk for PE. Filter retrieval potentially spares the longterm complications of permanent filters in younger trauma patients. Retrievable filters warrant consideration in patients who meet high-risk criteria for deep vein thrombosis or PE who cannot receive effective mechanical prophylaxis and in whom contraindications to anticoagulation are expected to be temporary.

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J Vasc Surg. 2004 Nov;40(5):965-70.
Pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis: safety and feasibility study.
Bush RL, Lin PH, Bates JT, Mureebe L, Zhou W, Lumsden AB.
Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA. rbush@bcm.tmc.edu

PURPOSE: The current standard of care for deep venous thromboembolism (DVT) is anticoagulation; however, this treatment method does not rapidly relieve clot burden or clinical symptoms. We describe a rapid and effective method of thrombus removal, with simultaneous percutaneous mechanical thrombectomy (PMT) and thrombolysis. METHODS: Over 26 months 20 patients (22 men, 2 women; mean age, 52 +/- 6 years [range, 38-79 years]) with extensive lower extremity DVT were treated with PMT with the AngioJet thrombectomy device in combination with lytic agent (urokinase, tissue plasminogen activator, or reteplase) added to the infusion. Three patients underwent treatment twice, because of recurrent DVT. The primary end point was angiographic evidence of restoration of venous patency at completion of the procedure. Complications, recurrent ipsilateral DVT, and improvement in clinical symptoms were evaluated. RESULTS: Complete thrombus removal was obtained in 15 procedures (65%), and partial resolution in the remaining 8 procedures (35%). Inciting occlusive lesions responsible for acute DVT were revealed in 14 patients (61%), and angioplasty with or without stenting was performed when necessary. In the 8 procedures with partial resolution additional catheter-directed thrombolysis was carried out on average for 5.7 hours, with further thrombus reduction. Overall, immediate (<24 hours) improvement in clinical symptoms was noted in 17 patients (74%). There were no complications related to either PMT or the short duration of lytic agent infusion. At average follow-up of 10.2 +/- 0.3 months (range, 3-26 months), 3 patients had recurrent ipsilateral DVT, and underwent repeat treatment. CONCLUSIONS: Addition of lytic agent to PMT facilitates thrombus extraction, decreases overall interventional treatment time, and improves patient outcomes. In addition, definitive management of underlying anatomic lesions can be performed in the same setting. Further outcome measures are necessary to study the long-term efficacy of this treatment method on preservation of valve function, reduction of chronic venous insufficiency, and improved quality of life.

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Neurosurg Focus. 2004 Oct 15;17(4):E6.
Prophylactic placement of an inferior vena cava filter in high-risk patients undergoing spinal reconstruction.
Rosner MK, Kuklo TR, Tawk R, Moquin R, Ondra SL.
Department of Neurological Surgery, Northwestern Memorial Hospital, Chicago, Illinois, USA. michael.rosner@na.amedd.army.mil

OBJECT: The purpose of this study was to evaluate the safety and efficacy of prophylactic inferior vena cava (IVC) filter placement in high-risk patients who undergo major spine reconstruction. METHODS: In the pilot study, 22 patients undergoing major spine reconstruction received prophylactic IVC filters. These patients were prospectively followed to evaluate complications related to the filter, the rate of deep venous thrombosis (DVT) formation, and the rate of pulmonary embolism (PE). These data were compared with those obtained in a retrospective review for PE in a matched cohort treated at the same institution. At a second institution the treatment guidelines were implemented in 17 patients undergoing complex spine surgery with the same follow-up criteria. In the pilot study, no patient experienced PE (0%), whereas two had DVT (9%). Bilateral DVT developed postoperatively in one patient (associated morbidity rate 4.5%), who required thrombolytic therapy. One patient died of unrelated surgical complications. The PE rate in the matched cohort at the same institution was 12%. At the second institution, no patient had PE, and no complications were noted. CONCLUSIONS: In this patient population, prophylactic IVC filter placement appears to decrease the PE rate substantially, from 12 to 0%. The placement of IVC filters appears to be a safe and efficacious intervention for prevention of PE in high-risk patients.

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Neurosurg Focus. 2004 Oct 15;17(4):E1.
Prophylaxis for deep venous thrombosis in neurosurgery: a review of the literature.
Browd SR, Ragel BT, Davis GE, Scott AM, Skalabrin EJ, Couldwell WT.
Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84132-2303, USA.

The incidence of deep venous thrombosis (DVT) and subsequent pulmonary embolism (PE) in patients undergoing neurosurgery has been reported to be as high as 25%, with a mortality rate from PE between 9 and 50%. Even with the use of pneumatic compression devices, the incidence of DVT has been reported to be 32% in these patients, making prophylactic heparin therapy desirable. Both unfractionated and low-molecular-weight heparin have been shown to reduce the incidence of DVT consistently by 40 to 50% in neurosurgical patients. The baseline rate for major intracranial hemorrhage (ICH) following craniotomy has been reported to be between 1 and 3.9%, but after initiation of heparin therapy this rate has been found to be as high as 10.9%. Therefore, neurosurgeons must balance the risk of PE against the increased risk of postoperative ICH from prophylactic heparin for DVT. The authors review the literature on the incidence of DVT and PE in neurosurgical patients, focusing on the incidence of ICH related to the use of unfractionated and low-molecular-weight heparin in this patient population.

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Pharmacotherapy. 2004 Oct;24(10 Pt 2):179S-183S.
The role of oral direct thrombin inhibitors in the prophylaxis of venous thromboembolism.
Hawkins D.
Mercer University Southern School of Pharmacy, Atlanta, Georgia 30341, USA.

Venous thromboembolism, which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. Two million people/year are affected by VTE, making it the third most common cardiovascular disease after coronary heart disease and stroke. The rationale for VTE prophylaxis stems from the clinically silent presentation of the disease and its prevalence among hospitalized patients. At greatest risk are patients undergoing major orthopedic surgery and those admitted to the intensive care unit with acute myocardial infarction, heart failure, ischemic stroke, respiratory disease, systemic infection, or other medical conditions that immobilize patients for 5 days or longer. Several anticoagulant regimens have been effective in reducing the risk of VTE after major orthopedic surgery. For patients undergoing total hip or knee replacement, treatment with adjusted-dose warfarin, low-molecular-weight heparins, or fondaparinux may be used. Warfarin, which has been around for more than 50 years, is the only oral anticoagulant available for VTE prophylaxis. Ximelagatran, a new low-molecular-weight oral prodrug of the direct thrombin inhibitor melagatran, has advantages over warfarin that may make it the drug of choice for prevention of VTE.

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Drugs. 2004;64 Suppl 1:27-35.
Clinical experience with ximelagatran in orthopaedic surgery.
Eriksson B.
Department of Orthopaedics, Sahlgrenska University Hospital/Ostra, Gothenburg, Sweden. b.eriksson@orthop.gu.se

Patients who undergo orthopaedic surgery are at substantially increased risk for venous thromboembolic events. These include proximal and distal deep vein thrombosis, with the former more likely to lead to pulmonary embolism and fatal complications. Anticoagulants are routinely used for venous thromboembolism prophylaxis in patients undergoing total hip or total knee replacement surgery. Although current treatments offer effective prophylaxis, they have disadvantages. Warfarin is limited by the requirement for coagulation monitoring to ensure effective and safe use. Similarly, low-molecular-weight heparins (LMWHs) have disadvantages, including the need for parenteral administration. This article brings together data from clinical trials of the novel oral direct thrombin inhibitor, ximelagatran, in the prevention of venous thromboembolism in patients undergoing elective total hip or total knee replacement. The ximelagatran clinical trial programme in orthopaedic surgery has focused primarily on five large multicentre studies in Europe (the Melagatran Thromboprophylaxis in Orthopaedic surgery II and III and Expanded Prophylaxis Evaluation Surgery Study studies) and in the United States (the Exanta Used to Lessen Thrombosis A and B studies), which enrolled more than 8000 patients. In addition, the USA clinical trial programme included three other trials that investigated ximelagatran in orthopaedic surgery; two of these studies focused on prevention of venous thromboembolism after total knee replacement, and one study investigated prevention of venous thromboembolism after total hip replacement. These studies compared ximelagatran with the LMWHs dalteparin and enoxaparin and with warfarin, and were designed to reflect regional differences in venous thromboembolism prophylaxis and to build on findings from previous studies. Generally, ximelagatran has been shown to possess comparable or greater efficacy relative to comparators. The timing and dose of ximelagatran have been shown to be important determinants of its efficacy and safety. As ximelagatran can be given in fixed oral dosing without coagulation monitoring, it is an attractive choice for the prevention of venous thromboembolism in major elective orthopaedic surgery.

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Drugs. 2004;64 Suppl 1:7-16.
Oral direct thrombin inhibition: an effective and novel approach for venous thromboembolism.
Haas S.
Institute for Experimental Oncology and Therapeutic Research, Technical University of Munich, Munich, Germany. sylvia.haas@lrz.tum.de

Venous thromboembolism is a serious illness that affects patient morbidity and mortality and presents a significant management challenge to healthcare providers world-wide. Despite major achievements in the significant reduction of thromboembolic complications, the most common therapies currently used for prevention and treatment of venous thromboembolism--heparins and vitamin K antagonists such as warfarin--have several limitations. In particular, unfractionated heparin and warfarin show significant inter-patient variability in pharmacokinetics and pharmacodynamics, which makes regular coagulation monitoring necessary. Furthermore, only warfarin is suitable for long-term use, as it is administered orally. A new class of anticoagulants has been developed that directly target thrombin, a key enzyme in the blood coagulation cascade. Unlike warfarin and heparin, these direct thrombin inhibitors are able to inhibit fibrin-bound thrombin and so produce more effective inhibition of coagulation. Importantly, some members of this class of drugs have been developed for oral administration. Ximelagatran, which is converted to its active form melagatran, has predictable pharmacokinetics and pharmacodynamics. Therefore, ximelagatran can be administered in fixed doses with no need for coagulation monitoring. Its efficacy and safety profile have been demonstrated in preclinical and clinical studies. As the first oral agent in the new class, direct thrombin inhibitors, ximelagatran has significant potential for improving the prevention and treatment of venous thromboembolism.

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J Vasc Surg. 2004 Oct;40(4):620-5.
Combined regional thrombolysis and surgical thrombectomy for treatment of iliofemoral vein thrombosis.
Blattler W, Heller G, Largiader J, Savolainen H, Gloor B, Schmidli J.

Objective In at least half of patients with iliofemoral deep vein thrombosis post-thrombotic syndrome develops when only anticoagulant therapy is given. We combined thrombolysis, applied under ischemic conditions,with surgical thrombectomy to restore patencyand valve function. The technique and the short-term and long-term results in 2 patient series are reported. Methods A catheter was inserted into a foot vein of the thrombosed leg, and the limb was excluded from the circulation with a pneumatic cuff placed on the thigh with the patient under general anesthesia. Urokinase (0.5 million-3 million IU) and heparin were infused and allowed to act for 30 minutes while the pelvic axis was cleared with a Fogarty catheter through an inguinal venotomy. The external iliac vein was then clamped and the cuff removed. Thrombi that detached from the wall were flushed out with reactive hyperemia and squeezed out with manual leg compression. The blood was retrieved, washed, and transfused back into the patient. Various additional procedures were performed to secure outflow. Two patient series are reported: 1 with 12 consecutive patients and 1 with 21 patients who were successfully treated 6 to 10 years previously. Follow-up data were obtained for all patients after 1 year and for 18 of 21 patients after 6 to 10 years. Patency and valve function were assessed with duplex scanning or venography. Studies of blood coagulation and the kinetics of urokinase were performed in 5 additional patients. Results Vein patency and valve function were restored in all consecutive patients. At 1 year none of the 33 patients had had recurrence, and none showed clinical signs of post-thrombotic syndrome. At 6 to 10 years 3 of 18 patients had experienced another venous thromboembolism, but none in the treated leg. Sixteen legs were asymptomatic without compression therapy, and 2 had venous claudication. Coagulation studies showed a trace concentration of urokinase and a mild decrease in fibrinogen in the systemic circulation. The concentration of urokinase in blood collected from the treated leg was only 1% of that infused. Conclusion Regional thrombolysis combined with surgical thrombectomy is relatively easy to perform and seems safe. Vein patency and valve function were restored, and post-thrombotic syndrome was prevented. Additional procedures to overcome pelvic vein obstructions were required in 11 of 33 patients (33%). The procedure should be tested against standard anticoagulation therapy in patients with acute iliofemoral thrombosis.

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Thromb Res. 2004;114(3):149-53.
An open-label, comparative study of the efficacy and safety of once-daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis.
Ramacciotti E, Araujo GR, Lastoria S, Maffei FH, Karaoglan de Moura L, Michaelis W, Sandri JL, Dietrich-Neto F; CLETRAT Investigators.
Hospital Cristovao da Gama, Rua Padre Vieira 326 Santo Andre SP 09070-720, Brazil. eramacciotti@yahoo.com

BACKGROUND: Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment of patients with proximal lower limb DVT. METHODS: 201 patients with proximal lower limb DVT from 13 centers in Brazil were randomized in an open manner to receive either enoxaparin [1.5 mg/kg subcutaneous (s.c.) OD] or intravenous (i.v.) UFH (adjusted to aPTT 1.5-2.5 times control) for 5-10 days. All patients also received warfarin (INR 2-3) for at least 3 months. The primary efficacy endpoint was recurrent DVT (confirmed by venography or ultrasonography), and safety endpoints included bleeding and serious adverse events. The rate of pulmonary embolism (PE) was also collected. Hospitalization was at the physician's discretion. RESULTS: Baseline patient characteristics were comparable between groups. The duration of hospital stay was significantly shorter with enoxaparin than with UFH (3 versus 7 days). In addition, 36% of patients receiving enoxaparin did not need to be hospitalized, whereas all of the patients receiving UFH were hospitalized. The treatment duration was slightly longer with enoxaparin (8 versus 7 days). There was a nonsignificant trend toward a reduction in the rate of recurrent DVT with enoxaparin versus UFH, and similar safety. CONCLUSIONS: A once-daily regimen of enoxaparin 1.5 mg/kg subcutaneous is at least as effective and safe as conventional treatment with a continuous intravenous infusion of UFH. However, the once daily enoxaparin regimen is easier to administer (subcutaneous versus intravenous), does not require aPTT monitoring, and leads to both a reduced number of hospital admissions and an average 4-day-shorter hospital stay.

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Circulation. 2004 Aug 31;110(9 Suppl 1):I27-34.
Invasive approaches to treatment of venous thromboembolism.
Augustinos P, Ouriel K.
Department of Vascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Deep vein thrombosis (DVT) occurs in one-quarter of a million individuals annually in the United States and results in significant disability from pulmonary embolism and chronic venous insufficiency, especially when the proximal iliofemoral is involved. Treatment has centered on early institution of adequate anticoagulation to prevent thrombus propagation and embolism, but anticoagulation alone does not always restore venous patency and many patients are left with venous outflow obstruction and valvular incompetence-the anatomic underpinnings of the postthrombotic syndrome. Various strategies have been used to restore patency of thrombosed veins, including open surgical thrombectomy, pharmacological thrombolysis, and percutaneous mechanical thrombectomy. Each modality has benefits and shortcomings. Surgical thrombectomy had previously been abandoned secondary to poor long-term results. More recently, with improved techniques and better patient selection, surgical thrombectomy has regained a therapeutic role in treating acute DVT in young patients with short segment occlusions. The advent of percutaneous techniques has allowed thrombolysis, percutaneous mechanical thrombectomy, and stenting to be used in conjunction with each other-allowing for better resolution of venous clot burden than when an individual modality is used alone. Practitioners who treat patients with DVT should be familiar with all the options available to restore venous patency, preserve valvular function, and thereby minimize the risk of late postthrombotic complications.

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Circulation. 2004 Aug 31;110(9 Suppl 1):I10-8.
Long-term management of patients after venous thromboembolism.
Kearon C.
Department of Medicine, McMaster University, McMaster Clinic, Henderson General Hospital, Hamilton, Ontario, Canada. kearonc@mcmaster.ca

Long-term treatment of venous thromboembolism (VTE) focuses mainly on the duration of anticoagulant therapy, usually with vitamin K (VK) antagonists. The duration of therapy should be individualized based on the risk of recurrent VTE if treatment were stopped and the risk of bleeding if treatment were continued. The risk of recurrence is low if thrombosis was provoked by a major reversible risk factor such as surgery; 3 months of treatment is usually adequate for such patients. The risk of recurrence is high if thrombosis was unprovoked ("idiopathic") or associated with an irreversible risk factor such as cancer; anticoagulant treatment for at least 6 months, and often indefinitely, is indicated for such patients. Risk of recurrence is intermediate if thrombosis was associated with a minor transient risk factor; such patients can be treated for 3 to 6 months. Within each of these categories, presentation as pulmonary embolism, >1 previous VTE, an underlying malignancy, an antiphospholipid antibody, or selected hereditary thrombophilic states favor more prolonged therapy, whereas isolated distal deep vein thrombosis, high risk of bleeding, and patient preference favor shorter treatment. The optimal intensity of anticoagulant therapy with VK antagonists corresponds to a target international normalized ratio of 2.5 (range, 2.0 to 3.0). Long-term treatment with low-molecular-weight heparin is an alternative to VK-antagonist therapy and is usually preferable in patients with active cancer. Oral direct thrombin inhibitors also appear suitable for long-term prevention of recurrent VTE but await regulatory approval and comparison with VK antagonists.

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Pharmacotherapy. 2004 Aug;24(8 Pt 2):120S-126S.
Anticoagulant prophylaxis in medical patients: an objective assessment.
Deitelzweig S, Groce JB 3rd; Heparin Consensus Group.
Ochsner Clinic Foundation, Section of Hospital-Based Internal Medicine, New Orleans, Louisiana 70121, USA. sdeitelzweig@ochsner.org

Venous thromboembolism (VTE) is a clinically silent and potentially fatal disease that manifests as deep vein thrombosis (DVT) and pulmonary embolism. Venous thromboembolism remains a serious public health challenge, with an ever-increasing odds ratio of occurrence given the aging population in the United States. This article reviews the epidemiology of VTE; risk factor identification and stratification as a means of advancing awareness, prevention, and detection of VTE; and prophylaxis options and their outcomes, particularly administration of unfractionated heparin (UFH) 5000 U subcutaneously every 12 versus 8 hours in the at-risk medical patient population. The important studies comparing outcomes of these different UFH dosing regimens compared with placebo and low-molecular-weight heparins also are discussed. Consensus recommendations shaping contemporary clinical practice guidelines in this setting are highlighted. A systemwide approach to treatment of all medical patients who are risk stratified and receiving appropriate pharmacologic prophylaxis is recommended.

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J Bone Joint Surg Br. 2004 Aug;86(6):809-12.
Prevention of deep-vein thrombosis after total hip and knee replacement. Low-molecular-weight heparin in combination with intermittent pneumatic compression.
Silbersack Y, Taute BM, Hein W, Podhaisky H.
Department for Orthopaedics and Physical Medicine, Martin Luther University, Halle/Salle, Germany.

After total hip (THR) or knee replacement (TKR), there is still an appreciable risk of developing deep-vein thrombosis despite prophylaxis with low-molecular-weight heparin (LMWH). In a prospective, randomised study we examined the efficacy of LMWH in combination with intermittent pneumatic compression in patients undergoing primary unilateral THR or TKR. We administered 40 mg of enoxaparin daily to 131 patients combined with either the use of intermittent pneumatic compression or the wearing of graduated compression stockings. Compression ultrasonography showed no evidence of thrombosis after LMWH and intermittent pneumatic compression. In the group with LMWH and compression stockings the prevalence of thrombosis was 28.6% (40% after TKR, 14% after THR). This difference was significant (p < 0.0001). In the early post-operative phase after THR and TKR, combined prophylaxis with LMWH and intermittent pneumatic compression is more effective than LMWH used with graduated compression stockings.

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Chest. 2004 Aug;126(2):501-8.
Superiority of fondaparinux over enoxaparin in preventing venous thromboembolism in major orthopedic surgery using different efficacy end points.
Turpie AG, Bauer KA, Eriksson BI, Lassen MR.
Department of Medicine, Hamilton Health Sciences-General Hospital, 237 Barton St East, Hamilton, ON, L8L 2X2, Canada. turpiea@mcmaster.ca

STUDY OBJECTIVES: To assess the relevance of various efficacy end points established for thromboprophylaxis trials, we compared the results of the fondaparinux phase III program in major orthopedic surgery using the original primary efficacy end point with those obtained when the efficacy end points recently suggested by the American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy and the European Committee for Proprietary Medicinal Products (CPMP) were used. SETTING AND PATIENTS: Fondaparinux was compared with enoxaparin in four multicenter, randomized, double-blind trials of major orthopedic surgery. The original primary efficacy end point consisted of a composite of deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or pulmonary embolism up to day 11. The efficacy end point established by the ACCP Consensus Conference on Antithrombotic Therapy comprises any proximal deep-vein thrombosis, symptomatic proven deep-vein thrombosis or pulmonary embolism, or fatal pulmonary embolism, and that established by the European CPMP comprises any proximal deep-vein thrombosis, symptomatic proven pulmonary embolism, or death from any cause. INTERVENTIONS: Patients were randomized to receive either subcutaneous fondaparinux (2.5 mg once daily) starting postoperatively or approved enoxaparin regimens. RESULTS: Using the original end point of the fondaparinux studies, the incidence of venous thromboembolism was 13.7% (371 of 2,703 patients) in the enoxaparin group compared with 6.8% (182 of 2,682 patients) in the fondaparinux group, with a common odds reduction of 55.2% (p = 10(-17); 95% confidence interval, 45.8% to 63.1%) in favor of fondaparinux. The respective incidences of efficacy end points with enoxaparin and fondaparinux were 3.3% and 1.7%, respectively, according to the ACCP definition, and 3.9% and 2.1%, respectively, according to the CPMP definition. The common odds reduction in favor of fondaparinux was 49.6% (p < 0.001) and 48.0% (p < 0.001), respectively. CONCLUSIONS: Fondaparinux was consistently more effective than enoxaparin in preventing venous thromboembolism in patients undergoing major orthopedic surgery, irrespective of the established composite outcomes used.

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Pharmacotherapy. 2004 Jul;24(7 Pt 2):82S-87S.
Evolving concepts in the treatment of venous thromboembolism: the role of factor Xa inhibitors.
Nutescu EA, Helgason CM.
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA. enutescu@uic.edu

Anticoagulation is an essential component of the care of patients with venous thromboembolism (VTE). Traditional anticoagulants for the treatment of VTE include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the oral vitamin K antagonist, warfarin. A variety of anticoagulant agents with improved pharmacologic and clinical profiles are emerging and offer benefits over the traditional therapies. One of the most recent advances has been the development of new agents, such as oral direct thrombin inhibitors and factor Xa inhibitors, that have a more selective and targeted effect on the coagulation cascade. Recent clinical trials have evaluated fondaparinux, the first commercially available factor Xa inhibitor, in the treatment of patients with deep vein thrombosis and pulmonary embolism and indicate efficacy and safety as compared with traditional options such as UFH and LMWH. Fondaparinux is a welcomed addition to the available antithrombotic options.

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Br J Surg. 2004 Jul;91(7):842-7. 

Randomized clinical trial of low molecular weight heparin with thigh-length or knee-length antiembolism stockings for patients undergoing surgery.
Howard A, Zaccagnini D, Ellis M, Williams A, Davies AH, Greenhalgh RM.
Department of Acute and Reconstructive Surgery, Imperial College of Science, Technology and Medicine, Charing Cross Hospital, London W6 8RF, UK.

BACKGROUND: This was a randomized clinical trial to determine the efficacy and safety of a 'blanket' protocol of low molecular weight heparin (LMWH) and the best length of antiembolism stocking, for every patient requiring surgery under general anaesthesia. METHODS: Of 426 patients interviewed, 376 agreed to be randomized to receive one of three types of stocking: thigh-length Medi thrombexin climax (Medi UK, Hereford, UK), knee-length thrombexin climax and thigh-length Kendall T.E.D. (Tyco Healthcare UK, Redruth, UK). All patients received LMWH thromboprophylaxis. Duplex ultrasonography was used to assess the incidence of postoperative deep vein thrombosis (DVT). RESULTS: No postoperative DVT occurred in 85 patients at low or moderate risk. Nineteen DVTs occurred, all in the 291 high-risk patients: two with the Medi thigh-length stockings, 11 with the Medi knee-length stockings (odds ratio 0.18 (95 per cent confidence interval 0.04 to 0.82); P = 0.026) and six with the Kendall T.E.D. thigh-length stockings. No patient developed a pulmonary embolism. Stocking groups were similar for age, sex, thromboembolic risk, type of operation and compliance. One significant bleeding complication occurred. CONCLUSION: A single protocol comprising LMWH and thigh-length stockings abolished DVT in low- and moderate-risk patients, and reduced the rate of DVT to 2 per cent in high-risk patients. Copyright 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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J Thromb Haemost. 2004 Jul;2(7):1058-70. 

Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis.
Mismetti P, Laporte S, Zufferey P, Epinat M, Decousus H, Cucherat M.
Department of Anesthesia, University Hospital Bellevue, Saint-Etienne, France.

BACKGROUND: The benefit-to-risk ratio of vitamin K antagonists (VKA), relative to active comparators, especially low-molecular-weight heparins (LMWH), for preventing venous thromboembolism in patients undergoing major orthopedic surgery is debated. OBJECTIVES: We performed a meta-analysis of all randomized trials in orthopedic surgery comparing adjusted doses of VKA to control treatments. PATIENTS AND METHODS: An exhaustive literature search, both manual and computer-assisted, was performed. Studies were selected on the basis of randomization procedure (VKA vs. a control group). At least one of the following outcome measures was to be evaluated: deep vein thrombosis (DVT), pulmonary embolism (PE), death, major hemorrhage or wound hematoma. Four reviewers assessed each article to determine eligibility for inclusion and outcome measures. RESULTS: VKAs were more effective than placebo or no treatment in reducing DVT [567 patients, relative risk (RR) = 0.56, 95% confidence interval (CI) 0.37, 0.84, P < 0.01] and clinical PE (651 patients, RR = 0.23, 95% CI 0.09, 0.59, P < 0.01). These results were obtained at the cost of a higher rate of wound hematoma (162 patients, RR = 2.91, 95% CI 1.09, 7.75, P = 0.03). VKAs were also more effective than intermittent pneumatic compression (534 patients, RR = 0.46, 95% CI 0.25, 0.82, P = 0.009) in preventing proximal DVT. In contrast, VKAs were less effective than LMWH in preventing total DVT and proximal DVT (9822 patients, RR = 1.51, 95% CI 1.27, 1.79, P < 0.001; and 6131 patients, RR = 1.51, 95% CI 1.04, 2.17, P = 0.028, respectively). The differences between VKA and LMWH in major hemorrhage and wound hematoma were not significant. CONCLUSIONS: In patients undergoing major orthopedic surgery, VKAs are less effective than LMWH, without any significant difference in the bleeding risk.

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Issues Emerg Health Technol. 2004 Jun;(58):1-4. 

Ximelagatran for prevention and treatment of venous thromboembolism.
Kwok L, Boucher M.

Ximelagatran (Exanta (TM)) is the first oral agent in a new class of anticoagulants called direct thrombin inhibitors. Most of the available evidence regarding venous thromboembolism is from studies focusing on its prevention after major orthopedic surgery. Ximelagatran's efficacy is comparable to that of warfarin and low-molecular-weight heparin in this setting. The rates of bleeding complications for ximelagatran and its comparators were not statistically different. The elevation of liver enzymes was observed in longer term trials.

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Am Fam Physician. 2004 Jun 15;69(12):2841-8. 

DVT and pulmonary embolism: Part II. Treatment and prevention.
Ramzi DW, Leeper KV.
Emory University School of Medicine, Atlanta, Georgia, USA.

Treatment goals for deep venous thrombosis include stopping clot propagation and preventing the recurrence of thrombus, the occurrence of pulmonary embolism, and the development of pulmonary hypertension, which can be a complication of multiple recurrent pulmonary emboli. About 30 percent of patients with deep venous thrombosis or pulmonary embolism have a thrombophilia. An extensive evaluation is suggested in patients younger than 50 years with an idiopathic episode of deep venous thrombosis, patients with recurrent thrombosis, and patients with a family history of thromboembolism. Infusion of unfractionated heparin followed by oral administration of warfarin remains the mainstay of treatment for deep venous thrombosis. Subcutaneously administered low-molecular-weight (LMW) heparin is at least as effective as unfractionated heparin given in a continuous infusion. LMW heparin is the agent of choice for treating deep venous thrombosis in pregnant women and patients with cancer. Based on validated protocols, warfarin can be started at a dosage of 5 or 10 mg per day. The intensity and duration of warfarin therapy depends on the individual patient, but treatment of at least three months usually is required. Some patients with thrombophilias require lifetime anticoagulation. Treatment for pulmonary embolism is similar to that for deep venous thrombosis. Because of the risk of hypoxemia and hemodynamic instability, in-hospital management is advised. Unfractionated heparin commonly is used, although LMW heparin is safe and effective. Thrombolysis is used in patients with massive pulmonary embolism. Subcutaneous heparin, LMW heparin, and warfarin have been approved for use in surgical prophylaxis. Elastic compression stockings are useful in patients at lowest risk for thromboembolism. Intermittent pneumatic leg compression is a useful adjunct to anticoagulation and an alternative when anticoagulation is contraindicated.

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Tech Vasc Interv Radiol. 2004 Jun;7(2):68-78.

Thrombolysis for lower extremity deep venous thrombosis.
Semba CP, Razavi MK, Kee ST, Sze DY, Dake MD.

Catheter-directed thrombolysis (CDT) has been proposed as an alternative mode of therapy to anticoagulation in patients with massive, symptomatic deep vein thrombosis of the extremity. The major goal of therapy is to rapidly restore venous blood flow, reduce the pain and edema of the extremity, preserve venous valve function, and reduce chronic symptoms related to chronic venous hypertension (postthrombotic syndrome). In patients with iliofemoral deep venous thrombosis (DVT) standard angiographic techniques are used to instrument a lower extremity vein (popliteal) and venography is performed followed by catheter-directed infusion of a plasminogen activator directly into the thrombus. Following lytic infusion, the interventionalist must evaluate the venous drainage to determine if there is an anatomic lesion that requires further endovascular treatment (eg, iliac vein compression syndrome). Posttreatment therapy usually consists of warfarin therapy and venous compression stockings for at least 3 to 6 months. The purpose of this article is to review the technical approach used in treating iliofemoral DVT and highlight the hurdles that face interventionalists in attempting to broaden this procedure to most types of lower extremity DVT.

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Tech Vasc Interv Radiol. 2004 Jun;7(2):63-7. 

Medical management of venous thromboembolic disease.
Deitelzweig S, Jaff MR.

Venous thromboembolic disease (deep vein thrombosis and pulmonary embolism) are common disorders with serious morbid and mortal complications. Given the varied modes of presentation, a high clinical index of suspicion in patients at risk must exist among physicians. Standard therapy has consisted of intravenous unfractionated heparin and overlapping administration of an oral Vitamin K antagonist, commonly Warfarin. Although an effective strategy, many practical limitations exist, including the need for prolonged hospitalization, frequent laboratory monitoring for anticoagulant effect, and erratic dose-response curves. Recently, subcutaneous low-molecular-weight heparins have emerged as safe and effective alternatives for unfractionated heparin. Appropriate patients may be treated with low-molecular-weight heparins and oral Warfarin entirely as outpatients, with similar efficacy and risk of recurrent thromboembolic events and hemorrhage. Thrombolytic therapy is a reasonable alternative in patients with iliofemoral venous thrombosis and/or pulmonary embolism resulting in hemodynamic compromise or obstructing significant pulmonary vasculature. Risks of serious hemorrhagic side effects including intracranial hemorrhage, along with the added economic burden, have limited widespread acceptance of thrombolytic therapy as primary treatment. Emerging oral direct thrombin inhibitors and other novel agents stand to move the treatment of patients with venous thromboemboli to even greater levels of safety and efficacy.

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BioDrugs. 2004;18(4):235-68. 

The role of recombinant hirudins in the management of thrombotic disorders.
Fischer KG.
Department of Medicine, University Hospital Freiburg, Freiburg, Germany.

Native hirudin is the most potent natural direct thrombin inhibitor currently known; it is capable of inhibiting not only fluid phase, but also clot-bound thrombin. Recombinant technology now allows production of recombinant hirudins (r-hirudins), which are available in sufficient purity and quantity with essentially unaltered thrombin-inhibitory potency.As thrombin is known to play a key role in a number of thrombotic disorders, numerous studies focused on the impact of r-hirudins on the clinical course in these diseases. R-hirudins provided significantly more stable anticoagulation than standard heparin, but demonstrated a relatively narrow therapeutic range with relevant bleeding risk even at clinically effective doses. In doses that are not associated with an increased bleeding risk, r-hirudins often failed to demonstrate significant superiority to heparin.To date, r-hirudins have a definite role in the treatment of heparin-induced thrombocytopenia, where they markedly reduce the high risk of thrombosis. For prophylaxis of deep vein thrombosis, r-hirudins have been shown to be superior to both unfractionated and low molecular weight heparin, but are not extensively used in this indication. In acute coronary syndromes, a definite role of r-hirudins has not yet been firmly established. When applied in an appropriate dose as adjunct to thrombolysis in patients with acute myocardial infarction, randomized, controlled trials did not show a consistent benefit of r-hirudins, especially in the long-term. In patients undergoing coronary balloon angioplasty for acute coronary syndromes, promising effects in the early postprocedural phase did not translate to an improved outcome after 6 months. In patients with unstable angina pectoris, efficacy and safety of r-hirudins as primary antithrombotic therapy are still under debate.In the future, r-hirudins are to be compared with alternative or additional potent antithrombotic agents or treatment strategies. This comparison will ultimately lead to their final placement in the management of thrombotic disorders.

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Drugs. 2004;64(14):1575-1596. 

Fondaparinux Sodium: A Review of its Use in the Prevention of Venous Thromboembolism Following Major Orthopaedic Surgery.
Reynolds NA, Perry CM, Scott LJ.
Adis International Limited, Auckland, New Zealand.

Fondaparinux sodium (Arixtra((R)); fondaparinux) is the first of a new class of synthetic pentasaccharide anticoagulants that bind to antithrombin and inhibit the action of factor Xa.In three large, well designed trials, subcutaneous fondaparinux 2.5mg once daily was more effective than subcutaneous enoxaparin sodium (enoxaparin) 30mg twice daily or 40mg once daily at preventing venous thromboembolism (VTE) at day 11 in patients undergoing hip replacement, elective major knee or hip fracture surgery; a fourth trial demonstrated similar efficacy to enoxaparin 30mg twice daily in hip replacement. Fondaparinux recipients had a lower incidence of proximal deep vein thrombosis (DVT) in two studies. In a meta-analysis of the four trials, patients receiving fondaparinux had a >50% reduction in the relative risk of VTE at day 11. Fondaparinux compared favourably with enoxaparin in several pharmacoeconomic analyses.In a large, controlled trial in hip fracture patients, extended prophylaxis with fondaparinux (duration 25-31 days) substantially reduced the incidence of VTE at day 25-32 compared with prophylaxis for 6-8 days, and was a cost-effective treatment strategy. Moreover, extended prophylaxis significantly decreased the rate of proximal, total and distal DVT and symptomatic VTE.Fondaparinux was generally well tolerated in clinical trials in patients undergoing major orthopaedic surgery. However, following major knee surgery and in a meta-analysis of pooled data from four trials, fondaparinux recipients had a significantly higher incidence of overt bleeding with a bleeding index >/=2, but no increase in fatal bleeding, bleeding into a critical organ or bleeding leading to reoperation. The bleeding risk is related to the timing of the first dose and when fondaparinux was initiated between 6 and 8 hours after surgery, the bleeding risk was similar to enoxaparin. Extended prophylaxis with fondaparinux was not associated with a significantly increased risk of bleeding events.In conclusion, fondaparinux is more effective than enoxaparin at preventing postoperative VTE in patients undergoing elective hip replacement, major knee or hip fracture surgery. Extended therapy with fondaparinux considerably increases its efficacy without a significant increase in the incidence of bleeding episodes. Fondaparinux was generally well tolerated in clinical trials. Fondaparinux is an effective and useful alternative to low molecular weight heparins for the prevention of VTE following major orthopaedic surgery.Pharmacological PropertiesFondaparinux sodium (fondaparinux), a synthetic pentasaccharide anticoagulant, selectively binds to antithrombin (AT), catalysing the inhibition of factor Xa. The in vitro antifactor Xa activity of fondaparinux is approximate, equals 700 anti-XaIU/mg.In vitro, fondaparinux does not bind to platelets or platelet factor 4 or inhibit platelet aggregation. It had no clinically significant effects on the activated partial thromboplastin time, prothrombin time, AT levels or the bleeding time in healthy volunteers.After subcutaneous injection, fondaparinux is rapidly and completely absorbed, and shows linear pharmacokinetics over a 2-8mg dose range in healthy volunteers. The volume of distribution (8.2-10.2L) suggests that drug distribution is limited to the vascular compartment only. In plasma, fondaparinux binds almost exclusively to AT.Fondaparinux is primarily excreted unchanged in the urine, with a correlation between clearance of fondaparinux and creatinine. In vitro studies suggest that fondaparinux does not undergo metabolism by liver enzymes and does not interfere with cytochrome P450-mediated metabolism of other drugs.Therapeutic EfficacyAt 11 days' follow-up, subcutaneous fondaparinux 2.5mg administered once daily for 5-9 days prevented venous thromboembolism (VTE) following major orthopaedic surgery in four large, well designed studies. Fondaparinux was more effective than standard prophylactic dosages of subcutaneous enoxaparin sodium (enoxaparin) at preventing postoperative VTE in patients undergoing electTE in patients undergoing elective hip replacement, major knee or hip fracture surgery. A meta-analysis showed that fondaparinux recipients had a &gt;50% relative risk reduction of VTE by day 11 compared with those receiving enoxaparin undergoing major orthopaedic surgery. Furthermore, secondary endpoint analysis showed that by day 11, patients receiving fondaparinux had a significantly lower rate of total or distal deep vein thrombosis (DVT) in all studies and proximal DVT in two trials than enoxaparin recipients.Prophylaxis with fondaparinux for 25&ndash;31 days after hip fracture surgery substantially reduced the incidence of VTE by day 25&ndash;32 compared with fondaparinux treatment for 6&ndash;8 days. Moreover, prolonged prophylaxis was associated with a lower incidence of proximal, total or distal DVT and fewer symptomatic VTEs than treatment for the standard duration.TolerabilityFondaparinux is generally well tolerated when used for the prophylaxis of VTE in patients undergoing major orthopaedic surgery. A meta-analysis of pooled data from the four trials in major orthopaedic surgery showed a significantly higher incidence of overt bleeding with a bleeding index &ge;2 with fondaparinux compared with enoxaparin, but no increase in fatal bleeding, bleeding into a critical organ or bleeding leading to reoperation.A low incidence of thrombocytopenia was seen in patients receiving fondaparinux (2&ndash;4.9%) or enoxaparin (3&ndash;5.3%). Thrombocytopenia was not reported as a serious adverse event in any trial, and no cases of heparin-induced thrombocytopenia were reported.No significant increase in the incidence of bleeding episodes was observed in patients receiving extended or standard-duration prophylaxis.Pharmacoeconomic StudiesFondaparinux compared favourably with enoxaparin in pharmacoeconomic studies in patients undergoing major orthopaedic surgery or elective major knee or hip fracture surgery. In patients undergoing hip replacement, fondaparinux was cost effective with respect to the incremental cost-effectiveness ratio per VTE avoided compared with enoxaparin 40mg once daily, but not 30mg twice daily. Fondaparinux was generally cost saving relative to enoxaparin at timepoints &ge;90 days after surgery. Extended prophylaxis with fondaparinux (duration of treatment 28 days) in patients undergoing surgery for hip fracture was also cost effective, and was cost saving relative to enoxaparin at timepoints &ge;90 days after surgery.

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J Vasc Interv Radiol. 2004 Jun;15(6):565-74. 

Pharmacomechanical thrombolysis and early stent placement for iliofemoral deep vein thrombosis.
Vedantham S, Vesely TM, Sicard GA, Brown D, Rubin B, Sanchez LA, Parti N, Picus D.
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. vendanthams@mir.wustl.edu

PURPOSE: To evaluate an approach to the treatment of iliofemoral deep vein thrombosis (DVT) that included pharmacomechanical catheter-directed thrombolysis with reteplase and the Helix mechanical thrombectomy device, followed by early stent placement. MATERIALS AND METHODS: During 3-year period, 23 symptomatic limbs in 18 patients with iliofemoral DVT were treated with reteplase catheter-directed thrombolysis. After an initial infusion of 8 to 16 hours, any residual acute thrombus over a long segment (> 10 cm) was treated by maceration with use of the Helix thrombectomy device. Residual short-segment (< 10 cm) iliac vein thrombus and/or stenosis were treated with stent placement. Technical success, clinical success, complications, thrombolytic infusion time, total thrombolytic agent dose, fibrinogen level changes, and late limb status were retrospectively analyzed. RESULTS: Technical success was achieved in 23 of 23 limbs (100%). Clinical success was achieved in 22 of 23 limbs (96%). Complete or partial thrombolysis was observed in 19 of 23 limbs (83%). Major bleeding was observed in one patient (6%) and necessitated blood transfusion. Mean per-limb thrombolytic infusion time and total dose were 19.6 hours +/- 8.1 and 13.8 U +/- 5.3 reteplase, respectively. Mean serum fibrinogen nadir and percentage drop in serum fibrinogen were 282 mg/dL +/- 167 and 47% +/- 24%, respectively. Late (mean, 19.8 +/- 11.6 months) modified Venous Disability Scores were 0 (none) for six limbs, 1 (mild) for 10 limbs, 2 (moderate) for two limbs, and 3 (severe) for no limbs. CONCLUSION: In a preliminary experience, pharmacomechanical catheter-directed iliofemoral DVT thrombolysis with early stent placement was safe and effective.

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Ann Intern Med. 2004 Jun 1;140(11):867-73. 

Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial.
Buller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, Prins MH, Raskob G, Segers AE, Cariou R, Leeuwenkamp O, Lensing AW; Matisse Investigators.
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

BACKGROUND: The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin). OBJECTIVE: To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis. DESIGN: Randomized, double-blind study. SETTING: 154 centers worldwide. PATIENTS: 2205 patients with acute symptomatic deep venous thrombosis. INTERVENTION: Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0. MEASUREMENTS: The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes. RESULTS: 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively. LIMITATIONS: Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients. CONCLUSIONS: Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.

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Angiology. 2004 May-Jun;55(3):243-9. 

Prevention of recurrent deep venous thrombosis with sulodexide: the SanVal registry.
Errichi BM, Cesarone MR, Belcaro G, Marinucci R, Ricci A, Ippolito A, Brandolini R, Vinciguerra G, Dugall M, Felicita A, Pellegrini L, Gizzi G, Ruffini M, Acerbi G, Bavera P, Renzo AD, Corsi M, Scoccianti M, Hosoi M, Lania M.
General Surgery Osp. Guardiagrele (Ch), University of Milan, Italy.

The aim of this study was to evaluate the prevention of recurrent deep vein thrombosis (R-DVT) with an oral antithrombotic agent (sulodexide) in moderate to high-risk subjects. A group of 405 patients was included into the multicenter registry. Both compression and an exercise program were used as well as a risk-factors control plan. After diagnosis of DVT, patients were treated with oral anticoagulants for 6 months. At the end of this period a coagulation study was made and patients started treatment with oral sulodexide capsules for a period of 24 months. The femoral, popliteal, tibial, and superficial veins were scanned with high-resolution ultrasound at inclusion;scans were repeated at 6, 12, 18, and 24 months. Of the 405 subjects included into the registry 178 in the control group (mean age 52.2; SD 11; M:F=90:88) and 189 in the treatment group (mean age 53.2; SD 10.3; M:F=93:96) completed the analysis period of 24 months. At 6 and 12 months the incidence of R-DVT was lower (p<0.05) in the treatment group. At 24 months the global incidence of R-DVT was 17.9% in the control group and 7.4% in the sulodexide group (p<0.05), 2.42 times lower than in controls. The 2 groups were comparable for age and sex distribution and for the localization of the thrombi at inclusion. Also the 2 groups of dropouts were comparable. In the control group there were 32 recurrent DVTs and 24 subjects lost to follow-up (total of 56) of 202 included subjects (27.7%) in comparison with 28 failures (14 recurrent DVTs and 14 lost subjects) of 203 subjects (13.8%) in the treatment group. This difference was statistically significant. In this analysis the incidence of DVT in controls was 2.07 times higher than in the treatment group subjects. In conclusion sulodexide was effective in reducing recurrent thrombotic events in high-risk subjects.

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Med Clin (Barc). 2004 May 8;122(17):641-7. 

[Bed rest or early mobilisation as treatment of deep vein thrombosis: a systematic review and meta-analysis]
[Article in Spanish]
Trujillo-Santos AJ, Martos-Perez F, Perea-Milla E.
Unidad de Medicina Interna, Hospital Costa del Sol, Marbella, 29007 Malaga, Spain. javiertrujillo@terra.es

BACKGROUND AND OBJECTIVE: We aimed to know if treatment of deep vein thrombosis (DVT) with early mobilisation is as safe and effective as bed rest. MATERIAL AND METHOD: MEDLINE, EMBASE, Cochrane library (CCTR), Spanish Medical Index, and MD-Consult Virtual Library databases were searched. We also cross-checked bibliographies of the retrieved articles. The TESEO database of doctoral theses in Spain was also revised. We only searched for clinical trial articles comparing bed rest with early mobilization with respect to the incidence of objectively diagnosed pulmonary embolism (PE) in patients treated for DVT of lower limbs. The concordance coefficient was evaluated by statistical methods. We used relative risk and 95% confidence intervals. Selection bias was evaluated using funnel plot. RESULTS: Only three articles were included in the metaanalysis, with 296 patients randomized from 773 patients initially evaluated, with a follow-up of 9 days to 3 months. Quality rating ranged from 61.4 to 90% and the kappa index of concordance ranged from 0.78 to 0.93. The relative risks of PE between the two groups of treatment (early mobilization versus bed rest) were 1.31 (0.63-2.72), 1.50 (0.17-13.23), and 1.45 (0.56-3.75), respectively, and the global RR was 1.37 (0.78-2.40). CONCLUSIONS: The analyzed studies reveal that the treatment of DVT with early mobilization rather than bed rest neither increases the rate of PE nor increases the complication rate. New well designed, controlled clinical trials are needed to confirm the conclusions of this review.

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Expert Rev Cardiovasc Ther. 2004 May;2(3):321-37. 

Clinical application of enoxaparin.
Hofmann T.
Universitatsklinikum Hamburg-Eppendorf, Herzzentrum, Medizinische Klinik III, Martinistr. 52, 20246 Hamburg, Germany. thofmann@uke.uni-hamburg.de

Low-molecular-weight heparins have several important advantages over unfractionated heparin (UFH). Due to a longer plasma half life together with high bioavailability and a linear dose-response relationship, the drugs can be safely and effectively administered in the hospital or ambulatory settings without the need to monitor the anticoagulant effect. Enoxaparin (Lovenox), Aventis Pharma) is a low-molecular-weight heparin which has been studied in a variety of clinical situations. In general surgery the efficacy of enoxaparin to prevent venous thromboembolism is similar to UFH but the tolerability is better. In patients undergoing cancer, orthopedic or vascular surgery the efficacy of enoxaparin is significantly higher with similar rates of bleeding complications. The database for enoxaparin in nonsurgical patients is smaller compared with surgical groups. There is evidence that the efficacy of enoxaparin may be superior to UFH in patients with severe cardiac disease. Efficacy and safety of UFH and enoxaparin are similar for the treatment of deep vein thrombosis. However, enoxaparin can be safely administered by the patients at home which is not possible with UFH. In patients with acute coronary syndromes, enoxaparin has been shown to reduce the rate of deaths and serious cardiac events in comparison with UFH. Furthermore, exonaparin treatment has been shown to be cost-effective, and therefore is the therapy of choice in this setting. In addition, enoxaparin has been shown to be a safe and effective alternative to the combination of UFH and phenprocoumone therapy in patients undergoing electrical cardioversion for atrial fibrillation.

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Int J Clin Pract. 2004 May;58(5):483-93. 

The design of venous thromboembolism prophylaxis trials: fondaparinux is definitely more effective than enoxaparin in orthopaedic surgery.
Turpie AG.
Department of Medicine, Hamilton Health Sciences-General Hospital, Hamilton, Ontario, Canada. turpiea@mcmaster.ca

The fondaparinux trials in venous thromboembolism (VTE) prevention after orthopaedic surgery have been subject to methodological criticisms recently summarised in this journal. These criticisms merit comments and corrections. Fondaparinux reduced the risk of VTE and of proximal deep-vein thrombosis by more than 55% compared with enoxaparin, based on the efficacy endpoint that supported the registration and use of low-molecular-weight heparins (LMWH) in all their prophylactic indications, an endpoint endorsed by international consensus statements and health authorities. Fondaparinux is the only antithrombotic agent that significantly reduced the rate of symptomatic VTE in a single orthopaedic surgery trial that was powered to detect this effect. In contrast to the paucity of data available on LMWH, the relationship between the timing of first administration and efficacy and safety has been well documented for fondaparinux. Fondaparinux used according to its approved regimen provides a simple, easy-to-use, effective and safe post-operative regimen for all orthopaedic surgery patients.

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Eur J Med Res. 2004 Apr 30;9(4):225-39. 

Low-molecular-weight heparin (LMWH) in the treatment of thrombosis.
Holzheimer RG.
University Halle-Wittenberg, Germany. Gresser.holzheimer@t-online.de

Thromboembolic complications are a common and costly medical problem, associated with significant morbidity and mortality, especially in postoperative patients. There have been reports of death due to thromboembolic complications even after short procedures, e.g. arthroscopy. Low-molecular-weight heparins (LMWHs) (e.g., certoparin, dalteparin, enoxaparin, nadroparin, reviparin, tinzaparin) have been tested for treatment of deep vein thrombosis in comparison to unfractionated heparin (UFH) in many patients being effective and safe alternative for treatment of deep vein thrombosis (DVT) and venous thromboembolism (VTE). Fixed-dose subcutaneous LMWH once daily is in most cases of equivalent efficacy and safety compared to conventional UFH therapy. There may be less risk for bleeding, less platelet activation together with a control of markers of haemostatic system activation, and either no progression or regression of thrombus size in patients treated with LMWH. The handling of LMWH is more comfortable for patients and less time consuming for nurses and laboratories compared to UFH. The cost-effectiveness analysis showed that LMWH are more cost effective than UFH. It has been calculated that outpatient treatment with LMWH may save 1641 dollars per patient in comparison to hospital treatment. This economic benefit of outpatient treatment of DVT seems to be realized in different health systems. Women with antiphospholipid antibodies and a history of either prior thrombotic events or pregnancy loss are at high risk during pregnancy for either another fetal death or thrombosis and may benefit from treatment with LMWH. In patients with malignant tumors secondary prophylaxis or long-term treatment with LMWH is successful. Patients with a contraindication for oral anticoagulants may benefit from treatment with LMWH as do patients on chronic anticoagulation treatment scheduled for an operative intervention. In most instances LMWH (dalteparin, enoxaparin, nadroparin) treatment for DVT may be given once daily at a fixed dose without any harm, based on a prolonged antithrombin activity. Effectiveness and safety of LMWH (dalteparin, enoxaparin, nadroparin, tinzaparin) in comparison to UFH treatment on outpatient basis has been demonstrated in several studies. In summary, LMWHs have an established role in the treatment of DVT and pulmonary embolism (PE), on an in- and outpatient basis and could realize substantial savings. Most studies were performed with dalteparin, enoxaparin and nadroparin. There is evidence that LMWHs may help to prolong survival in cancer patients and to avoid complications of the acute coronary syndrome.

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J Vasc Interv Radiol. 2004 Apr;15(4):347-52.
Comparison of Urokinase, Alteplase, and Reteplase for Catheter-directed Thrombolysis of Deep Venous Thrombosis.
Grunwald MR, Hofmann LV.
Division of Vascular and Interventional Radiology, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Blalock 545, 600 N. Wolfe Street, Baltimore, Maryland 21287.

PURPOSE: To compare the efficacy, safety, and costs associated with catheter-directed thrombolysis with urokinase (UK) and the recombinant agents alteplase (tissue plasminogen activator [TPA]) and reteplase (recombinant plasminogen activator [RPA]) in the treatment of symptomatic deep vein thrombosis (DVT). MATERIALS AND METHODS: The authors conducted a retrospective analysis on 74 patients (82 limbs) who underwent treatment for DVT. Thrombosed extremities were treated with either urokinase with therapeutic heparin dosing (UK group; 38 limbs), alteplase with subtherapeutic heparin dosing (TPA group; 32 limbs), or reteplase with subtherapeutic heparin dosing (RPA group; 12 limbs). Infusion times, dosages, drug costs, success rates, and complications were compared among the groups. RESULTS: Gender, age, disease location, duration of symptoms, and use of additional interventional therapies did not differ statistically among the three cohorts. Median hourly infused doses, total doses, infusion times, drug costs, and success rates per limb were: UK, 11.3 (10(4)) U/hour, 4.361 million U, 40.6 hours, $6577, 97.4%; TPA, 0.57 mg/hour, 21.6 mg, 30.8 hours, $488, 96.9%; RPA, 0.74 U/hour, 21.4 U, 24.3 hours, $1787, 100.0%. Major and overall complication rates were: UK, 5.3% and 10.5%; TPA, 3.1% and 12.5%; RPA, 8.3% and 16.7%. Infusion times, success rates, and complications were not statistically different among the three groups. Alteplase and reteplase were significantly less expensive than urokinase (P <.001 and P <.01, respectively). CONCLUSION: Catheter-directed thrombolysis for the treatment of DVT is safe and effective, regardless of the agent used. However, the new recombinant agents are significantly less expensive than urokinase.

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Curr Treat Options Cardiovasc Med. 2004 Apr;6(2):151-158.
Treatment of Venous Thromboembolism in Pregnancy.
Chan WS.
Department of Medicine, University of Toronto, Women's College Ambulatory Care Centre, Sunnybrook and Women's College Health Sciences Centre, 76 Grenville Street, Toronto, Ontario M5S 1B2, Canada. wee-shian.chan@sw.ca

Venous thromboembolism is a major preventable cause of maternal mortality in developed countries. Following objective diagnosis of deep vein thrombosis or pulmonary embolism, appropriate treatment with anticoagulation should be initiated. The therapeutic options in pregnancy are limited to the use of either unfractionated heparin or low molecular weight heparin. Oral anticoagulants, like warfarin, are relatively contraindicated for use during pregnancy for the treatment of venous thromboembolism because they freely cross the placenta and can be associated with adverse fetal effects. The appropriate length of treatment for acute venous thromboembolic disease diagnosed during pregnancy should be at least 3 months and possibly up till 6 weeks after delivery.

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J Vasc Interv Radiol. 2004 Mar;15(3):249-56.
Acute iliofemoral deep vein thrombosis: evaluation of underlying anatomic abnormalities by spiral CT venography.
Chung JW, Yoon CJ, Jung SI, Kim HC, Lee W, Kim YI, Jae HJ, Park JH.
Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, Clinical Research Institute, Seoul National University Hospital, Korea. chungjw@radcom.snu.ac.kr

PURPOSE: To evaluate the spectrum of underlying anatomic abnormalities in iliofemoral deep vein thrombosis (DVT) by spiral computed tomographic (CT) venography. MATERIALS AND METHODS: During the past 4 years, 56 patients with acute iliofemoral DVT have been evaluated by CT venography at our institution. Forty-four patients had left-sided DVT, nine had right-sided DVT, and the remaining three had DVT in both extremities. CT venography was performed with use of 2.5-3.2-mm x-ray beam collimation and a 1.25-2.0-mm reconstruction interval. Spiral scans were initiated 5 minutes after intravenous contrast medium injection. The CT venograms were correlated with catheter venograms. In addition, with use of axial sections and their three-dimensional reconstructions, including multiplanar reformation and volume rendering, the presence or absence of central obstructing lesions and their causes were evaluated. RESULTS: Among 44 patients with left-sided DVT, 37 had significant anatomic abnormalities in their iliofemoral veins or inferior vena cava (IVC). The most common lesion was left common iliac vein compression by the right common iliac artery (n = 27; exaggerated by a bony spur in nine and associated with extrinsic compression by the left internal iliac artery in two). Of the nine patients with right-sided DVT, six had significant anatomic abnormalities including encasement or extrinsic compression of their iliac veins by various causes (n = 3) and venous stricture without extrinsic lesions (n = 3). Among three patients with DVT in both extremities, two had anatomic abnormalities in the IVC. Therefore, 45 of 56 patients had anatomic abnormalities central to the thrombosed deep veins. CONCLUSION: The majority of patients with acute iliofemoral DVT had underlying anatomic abnormalities. The presence of central stenosis or obstruction and their causes can be evaluated by spiral CT venography.

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J Thromb Haemost. 2004 Mar;2(3):441-4.
Incidence and prognosis of cancer associated with bilateral venous thrombosis:
a prospective study of 103 patients.
Bura A, Cailleux N, Bienvenu B, Leger P, Bissery A, Boccalon H, Fiessinger JN, Levesque H, Emmerich J.
Service de Medecine Vasculaire-HTA and INSERM U428, Hopital Europeen Georges Pompidou, Paris, France.

Background: A strong association between bilateral deep vein thrombosis (DVT) and cancer had been found in one retrospective study. To confirm this finding, consecutive patients with an objective diagnosis of bilateral DVT were followed over 12 months. Patients and methods: One-hundred and three patients, hospitalized for bilateral DVT, were included in the study. Twenty-six patients (25.2%) were already known to have a cancer, 26 (25.2%) had a previous history of venous thromboembolic disease, 44 (42.7%) had a symptomatic pulmonary embolism. The patients were scheduled to be prospectively followed up at 3, 6 and 12 months as outpatients. Information on recurrence, evidence of a new overt cancer and the cause of death were recorded for all patients. Results: A new cancer was diagnosed in 20 (26%) of the 77 patients without known cancer at admission. The risk of cancer was significantly more important in idiopathic thrombosis than in patients with secondary thrombosis (40.5% vs. 12.5%; odds ratio 4.8, 95% confidence interval 1.4, 18.8). Seventy percent of the cancers discovered had already spread. Age, gender, presence of pulmonary embolism, recurrence and location of the thrombosis were not statistically associated with the risk of cancer. The 1-year survival rates of patients with a previously known cancer and patients with a newly discovered cancer were, respectively, 26% and 35% (P = 0.33). Conclusion: Bilateral DVT is a significant risk indicator of malignancy. Cancer is present in 45% of patients with bilateral DVT and is associated with a poor prognosis.

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Eur Radiol. 2004 Feb 26 [Epub ahead of print]
Diagnosis and management of deep vein thrombosis of the upper extremity: a review.
Baarslag HJ, Koopman MM, Reekers JA, Van Beek EJ.
Department of Radiology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Deep vein thrombosis of the upper extremity is an increasing clinical problem due to the use of long-term indwelling catheters for chemotherapy or long-term feeding. The clinical diagnosis is difficult to make, and various imaging modalities have been used for this purpose. The use of (interventional) radiological procedures has been advancing in recent years. This review describes the clinical background, the imaging modalities that may be employed, treatment options and outcome of patients with upper extremity thrombosis.

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Tunis Med. 2003 Nov;81(11):847-53.
[Home treatment of venous thrombosis. "For and against"]
[Article in French]
Ben Khalfallah A, Annabi N.
Service de Cardiologie, Hopital Menzel Bourguiba, Tunisie.

The ambulatory treatment of venous thromboses is made possible since the avenement of the low molecular weight heparins, which ensures an efficacy and a safety, comparable with the infractioned heparins, with less side effects and hemorrhagic complications. The simplicity of the therapeutic diagram with the low molecular weight heparin, the biological monitoring less astringent as well as the reduction of the cost of the treatment constitute solid arguments in favour of this therapeutic modality. The essential condition for such attitude remains the respect of the indications and of counter indications.

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Thromb Haemost. 2004 Mar;91(3):538-43.
Is prolonged immobilization a risk factor for symptomatic venous thromboembolism in elderly bedridden patients? Results of a historical-cohort study.
Gatt ME, Paltiel O, Bursztyn M.
Department of Medicine, Hadassah- Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91120, Israel. gatt@md.huji.ac.il

Prolonged immobilization and advanced age are considered to be important risk factors for venous thromboembolism (VTE). Nevertheless, the need for VTE prophylaxis in long-term bedridden patients is not known. To assess whether very prolonged immobilization (i.e. over three months) carries an increased risk for clinically apparent VTE, we performed a historical-cohort study of nursing home residents during a ten-year period. Data concerning patient's mobility and incidence of overt deep vein thrombosis or pulmonary embolism were registered. The mean resident age was 85+/-8.4 years. Eighteen mobile and eight immobile patients were diagnosed with clinically significant thromboembolic events, during 1137 and 573 patient-years of follow up, respectively. The incidence of venous thromboembolic events was similar in both chronically immobilized and mobile patient groups, 13.9 and 15.8 per thousand patient years, respectively (p=0.77). The rate ratio for having a VTE event in the immobilized patient group as compared with the mobile group was 0.88 (95% Confidence Interval (CI) 0.33 to 2.13). When taking into account baseline characteristics, risk factors and death rates by various causes, no differences were found between the two groups. In conclusion, chronically immobile bedridden patients are no more prone to clinically overt venous thromboembolic events than institutionalized mobile patients. Until further studies are performed concerning the impact of very prolonged immobilization on the risk of VTE, there is no evidence to support primary prevention after the first three months of immobilization. Evidence for efficacy or cost effectiveness beyond this early period is not available.

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Curr Control Trials Cardiovasc Med. 2004 Feb 18;5(1):1.
Effects of oral anticoagulation with various INR levels in deep vein thrombosis cases.
Yetkin U, Karabay O, Onol H.
Izmir Ataturk Education and Research Hospital, Department of Cardiovascular Surgery, TURKEY. ozalp.karabay@deu.edu.tr

AIM: In order to avoid the complications associated with thromboembolic disease, patients with this condition typically are placed on long-term anticoagulant therapy. This report compares bleeding complications in this patient population by level of achieved INR. MATERIALS AND METHODS: During the 6-year period between January 1997 and January 2003, 386 patients with venous thromboembolism of the lower extremities were admitted to the Cardiovascular Surgery Outpatient Clinic of Alsancak State Hospital. Of the 386 patients, 198 (51.2%) were women, and the average age was 52.3 years. All diagnoses of venous thromboembolism were confirmed by means of Doppler ultrasonography. Further investigation showed occult neoplasms in 22 (5.6%) of the cases. We excluded the patients with occult disease, and the remaining 364 constituted our study population. RESULTS: Oral anticoagulation was standardized at 6 months' duration in all cases. We divided the patients into two groups. Group I consisted of 192 patients (52.7%) with INR values between 1.9 and 2.5; Group II comprised 172 patients with INR values between 2.6 and 3.5. Complications in each group were assessed and compared. The minor hemorrhage rate was 1.04% in Group I and 4.06% in Group II. The major hemorrhage rate was also 1.04% in Group I and was 6.3% in Group II. We determined that the complication rates for both minor and major hemorrhage were significant in patients with INR values above 2.5. CONCLUSION: Oral anticoagulation must be followed closely in patients with venous thromboembolism. Higher INR levels are associated with significant increases in hemorrhage and associated complications. INR values of 2.0 to 2.5 are sufficient for long-term anticoagulant therapy, ensuring ideal anticoagulation levels and minimizing the complication rate.

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N Engl J Med. 2003 Aug 14;349(7):631-9.
Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism.
Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, MacKinnon B, Weitz JI, Crowther MA, Dolan S, Turpie AG, Geerts W, Solymoss S, van Nguyen P, Demers C, Kahn SR, Kassis J, Rodger M, Hambleton J, Gent M; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators.
McMaster University, Hamilton, Ont.

BACKGROUND: Warfarin is very effective in preventing recurrent venous thromboembolism but is also associated with a substantial risk of bleeding. After three months of conventional warfarin therapy, a lower dose of anticoagulant medication may result in less bleeding and still prevent recurrent venous thromboembolism. METHODS: We conducted a randomized, double-blind study, in which 738 patients who had completed three or more months of warfarin therapy for unprovoked venous thromboembolism were randomly assigned to continue warfarin therapy with a target international normalized ratio (INR) of 2.0 to 3.0 (conventional intensity) or a target INR of 1.5 to 1.9 (low intensity). Patients were followed for an average of 2.4 years. RESULTS: Of 369 patients assigned to low-intensity therapy, 16 had recurrent venous thromboembolism (1.9 per 100 person-years), as compared with 6 of 369 assigned to conventional-intensity therapy (0.7 per 100 person-years; hazard ratio, 2.8; 95 percent confidence interval, 1.1 to 7.0). A major bleeding episode occurred in nine patients assigned to low-intensity therapy (1.1 events per 100 person-years) and eight patients assigned to conventional-intensity therapy (0.9 event per 100 person-years; hazard ratio, 1.2; 95 percent confidence interval, 0.4 to 3.0). There was no significant difference in the frequency of overall bleeding between the two groups (hazard ratio, 1.3; 95 percent confidence interval, 0.8 to 2.1). CONCLUSIONS: Conventional-intensity warfarin therapy is more effective than low-intensity warfarin therapy for the long-term prevention of recurrent venous thromboembolism. The low-intensity warfarin regimen does not reduce the risk of clinically important bleeding. Copyright 2003 Massachusetts Medical Society

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Am Surg. 2003 Aug;69(8):635-42.
The role of vena caval filters in the management of venous thromboembolism.
Jacobs DG, Sing RF.
Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina 28203, USA.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are important, and not infrequent, causes of morbidity and mortality in critically ill patients. Anticoagulation remains the treatment of choice for DVT and PE, but contraindications to, and complications from, anticoagulant therapy mandate the availability of alternate therapeutic and prophylactic strategies. The recent availability of safe and effective vena caval filters that can be inserted via a minimally invasive percutaneous approach has expanded the indications for, and acceptance of, these devices in selected patients at high risk for the development of PE. This article reviews both the established and the evolving indications for vena caval filters and discusses how improvements in filter design may impact future use.

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Am Surg. 2003 Aug;69(8):654-9.
Complications of inferior vena cava filters.
Joels CS, Sing RF, Heniford BT.
Department of General Surgery, Carolinas Medical Center, Charlotte, North Carolina 28203, USA.

Inferior vena cava (IVC) filters offer a safe and effective means of preventing pulmonary embolus and have reduced complications when compared to earlier techniques of caval interruption. However, despite continued improvement in filters and insertion methods, complications still occur. Pneumothorax, hemorrhage, and vessel injury may result while obtaining vascular access. Filter misplacement, excessive tilt, and vascular injury have been reported with insertion, but preinsertion cavography is helpful in preventing these insertion-related complications. Attention to detail, proper use of guidewires, and preinsertion imaging are vital in preventing insertion-related complications as well. Long-term complications occur in a minority of patients and include recurrent pulmonary embolus, caval occlusion, and filter migration. Overall, the benefits of preventing pulmonary embolism far exceed the risks related to filter placement in properly selected patients.

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Expert Opin Drug Saf. 2003 Jan;2(1):87-94.
Safety of low molecular weight heparins in the treatment of venous thromboembolism.
Bernardi E, Prandoni P.
Pronto Soccorso, Azienda Ospedaliera di Padova, Via Giustiniani, n.1, 35128 - Padova, Italy. enriberni@hotmail.com

Low molecular weight heparins (LMWHs) are commonly employed as a substitute for unfractionated heparin (UFH) in the treatment of venous thromboembolic events. Despite their higher cost, the preferential use of LMWHs seemed justified initially as, based on the results of earlier meta-analyses, these compounds were deemed to be more effective and safer than UFH. Although, in this respect, their purported superiority over UFH could not be confirmed by subsequent large, randomised trials and updated meta-analyses, other peculiar features of LMWHs were highlighted, favouring their preferential utilisation in patients with venous thromboembolism. Among these, the possibility of once-daily administration on an out-patient basis, the lower incidence of Type II heparin-induced thrombocytopenia and the lower likelihood of osteoporosis after prolonged treatment periods, appear to be especially prominent. This review attempts to evaluate the available evidence focusing on the safety of LMWHs for the treatment of venous thromboembolism and the current therapeutic options and potential advantages of LMWHs, either in general or in selected patient populations.

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Klin Khir. 2003 Mar;(3):44-8.
[Acute thrombosis of lower extremities. Risk factors, methods of prevention and treatment]
[Article in Russian]
Gubka AB, Pertsov VI, Gubka VA, Karnaukh LP, Buga DA.

The results of treatment of 526 patients with an acute venous thrombosis of the lower extremities aged from 23 to 70 years, including 140 (36.3%) men and 376 (63.7%) women, were analyzed. The main etiological factors of thrombosis were physical overload, operations with subsequent immobilization, trauma of lower extremities, pregnancy and delivery, tumor of small pelvis and of other localization. In 65 patients an acute venous thrombosis was complicated by thromboembolism of pulmonary artery (TEPA), 2 patients died before initiation of treatment. Conduction of conservative therapy in 314 (94.4%) patients with thrombosis of the lower extremities deep veins using fraxiparine (fraxiparine forte) have allowed to achieve considerable improvement of their state. In 80 patients with thrombosis of subcutaneous veins was performed ligature of mouth for prophylaxis of TEPA, in all of them good clinical result was noted. High efficacy of fraxiparine application in prophylactical dosage for prevention of the venous thromboembolism occurrence was noted.

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Angiol Sosud Khir. 2003;9(1):61-5.
[The problem of postoperative venous thromboembolic complications in general surgery]
[Article in Russian]
Kirienko AI, Mishnev OD, Tsitsiashvili MSh, Agafonov VF.
Pediatric Department, Medical University, Moscow, Russia.

The paper reviews occurrence, diagnostic tools venous thromboembolic complications. Cost effectiveness of preventive measures for venous thrombosis and pulmonary embolism in general surgery is analysed. The study included 45 patients who underwent elective (21) and urgent (24) abdominal and pelvic interventions. Each patient was examined with ultrasonic with color Doppler imaging before and 8-10 days after surgery. Deep venous thrombosis of lower limbs was diagnosed in 11.1%, most of cases being asymptomatic. Ultrasonic angioscanning appeared to be an acute and reliable diagnostic tool for this pathology. Various approaches to the management of patients at thrombotic risk are reviewed. Cost effectiveness analysis of anticoagulation prevention for postoperative venous thromboembolic complications must address the problem: is prevention outcome worth those extra efforts? Surveillance of 500 patients at high thrombotic risk has shown that preventive use of low weight heparin (Clexane) is economically beneficial then conventional Heparin, the more in the absence of special preventive strategy. Targeted prevention in patients with different risk of postoperative venous thromboembolic complications can yield more then 3-fold reduction in occurrence of these complications.

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Tech Vasc Interv Radiol. 2003 Mar;6(1):49-52.
Mechanical thrombectomy for the treatment of lower extremity deep vein thrombosis.
Frisoli JK, Sze D.
Cardiovascular and Interventional Radiology, Stanford University Hospital, Stanford, CA 94305-5642, USA.

Deep venous thrombosis (DVT) has potentially debilitating long-term sequelae if left untreated. Conventional treatment (systemic anticoagulation with heparin followed by coumadin or low molecular weight heparin) often does not adequately relieves clot burden or symptoms, and patients may be left with post-thrombotic syndrome. Although the advent of catheter-directed thrombolysis has markedly improved the treatment of DVT and long-term outcomes of patients treated for DVT, it remains only partially effective on subacute or chronic clot. Mechanical thrombolysis may work synergistically with catheter-directed thrombolysis to decrease clot burden, treatment time, and complication rates, thereby improving outcomes. Copyright 2003 Elsevier Inc. All rights reserved.

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An Med Interna. 2003 Mar;20(3):134-6.
[Treatment of deep vein thrombosis with low molecular weight heparins at home]
[Article in Spanish]
Suarez Alvarez CG, Garcia Canete J, Herrero Mendoza MD, Bellver Alvarez TM, Arboiro Pinel R.
Unidad de Hospitalizacion a Domicilio, Clinica Ntra. Sra. de la Concepcion, Fundacion Jimenez Diaz, Avda. Reyes Catolicos, 2. 28040 Madrid.

Treatment of patients with proximal vein thrombosis with low molecular weight heparins is effective and safe. So it allows "hospital at home" care. Among low molecular weight heparins tinzaparin is given once daily, making the compliance easier. The twenty patients with deep vein thrombosis who were assisted in the "hospital at home" unit of the Clinica Nuestra Senora de la Concepcion in Madrid from December 1999 to December 2000. The mean of age was 71 + 15. The most frequent risk factors were surgery in past three months (19%), known tumour (15%) and previous venous thrombosis (15%). Eighteen patients were treated with tinzaparin. No patients showed adverse effects nor complications. Low molecular weight heparins, specially tinzaparin, are a safe and effective treatment for deep vein thrombosis in our unit.

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J Am Board Fam Pract. 2003 May-Jun;16(3):246-50.
When deep venous thrombosis fails to respond to therapy.
LaPorte D, Farber S, Sorin S, Wabba S, Daneels E, Korzenko A, Kopes-Kerr CP.
Department of Family Medicine, State University of New York at Stony Brook, 11794, USA.

BACKGROUND: Deep venous thrombosis in primary care is usually treated with rest, analgesics, intravenous or low-molecular-weight heparin, and coumadin. In some cases, however, a less familiar course of diagnosis and management is required. METHODS: We describe the case of a 53-year-old truck driver who had an acute deep venous thrombosis of his right lower extremity, which failed to respond to routine therapy with heparin and warfarin. A literature search was undertaken to research the differential diagnosis and management of deep venous thrombosis and to review specifically the role of venal caval filters and inherited thrombotic disorders and occult cancer in this context. RESULTS AND CONCLUSION: The ultimate diagnosis in our patient appeared to be signet ring cell cancer of the colon that had metastasized to the right thigh. This case is an example of the inherent limitations of even an aggressive diagnostic and therapeutic approach to the entity of refractory deep venous thrombosis.

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Curr Opin Investig Drugs. 2003 Mar;4(3):309-15.
Recent advances in the diagnosis and treatment of deep vein thrombosis: a regional consensus.
Qari M, Abdel-Razeq H, Alzeer A, Alizadeh H, Kristensen J, al-Sayegh F, Qutub H, Marashi M, Husted S, Mousa S.
Department of Hematology, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. drqari@hotmail.com

Considerable progress has been made in the understanding of the risk factors for venous thromboembolism (VTE). The clinical applications of molecular techniques have allowed identification of important inherited, yet not uncommon, risk factors for VTE, such as mutations that cause Factor V Leiden and prothrombin G20210A. However, advances in our understanding have raised several questions regarding the need for, and duration of anticoagulation. At the end of the treatment period, low molecular weight heparins have become the drugs of choice and standard-of-care for VTE. In this review, cost effective diagnostic approaches for patients with suspected deep vein thrombosis, and recommended treatment options using evidence-based approaches, are described.

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Expert Opin Investig Drugs. 2003 May;12(5):865-70.
The METHRO trials.
Hamaad A, Tayebjee MH, Lip GY.
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, B18 7QH, UK.

Venous thromboembolism is a common and potentially fatal complication among hospital in-patients, particularly those undergoing orthopaedic surgery. Current prophylactic strategies utilise low molecular weight heparins (LMWHs) and warfarin. However, painful subcutaneous injections for LMWHs and delays in achieving target anticoagulation for warfarin pose significant problems clinically. The Melagatran for THRombin inhibition in Orthopaedic surgery (METHRO) trial represents a landmark step in the sequential combination of subcutaneous and oral anticoagulation with melagatran and ximelagatran, respectively, for surgical venous thromboprophylaxis. These agents have proven to be as effective and safe as LMWHs. Furthermore, with no need for dosage adjustment or therapeutic drug monitoring there is emerging evidence that ximelagatran may replace warfarin as the anticoagulant of choice.

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J South Orthop Assoc. 2003 Spring;12(1):10-7.
Postoperative deep vein thrombosis prophylaxis: a retrospective analysis in 1000 consecutive hip fracture patients treated in a community hospital setting.
Ennis RS.
University of Miami, School of Medicine, USA. rsennismd@orthomed.us

The occurrence of deep vein thrombosis (DVT) following cases of major trauma, in particular pelvic and hip fracture, has ranged from 36% to 60%, depending on the study quoted and the method of detection. The frequency of fatal pulmonary embolism (PE) has been reported as 0.5%-12.9% of the cases. A retrospective study of 1000 consecutive hip fracture patients in a community hospital setting reveals that 95% received a combination of mechanical and pharmacologic prophylaxis for prevention of DVT. Sixty-one patients were excluded for insufficient data, leaving 939 for analysis. There were 724 female patients with an average age of 83 years and 215 male patients with an average age of 78 years. Fifty-one patients (18.4%) received no prophylaxis in the eligible population. Three hundred eighty-seven patients (41.2%) received only aspirin as the pharmacologic agent for anticoagulation. Four hundred twenty-nine patients (45.6%) were treated with the low-molecular-weight heparin (LMWH), enoxaparin. Ten patients (1.1%) received heparin for anticoagulation and 17 patients (1.8%) were treated with warfarin. A total of 43 patients received a combination of therapies. Four hundred ninety-five of the patients used concomitant intermittent pneumatic compression in addition to pharmacologic prophylaxis. There were 15 perioperative deaths from all causes, including five cases of DVT two distal and three proximal). One distal DVT occurred prior to surgery. A second distal DVT and one fatal PE occurred in the aspirin group. The rates of minor bleeding complications in the aspirin group, the < 12-hour postoperative dosing of the enoxaparin group, and the 12 to 24-hour postoperative dosing of the enoxaparin group were 3.1%, 5.7%, and 2.8%, respectively. There were no major bleeds in the aspirin group and 0.9% in the enoxaparin group. The LMWH group also had two proximal DVTs but no PEs. The combination of a relatively short half-life, predictable pharmacokinetics, and favorable safety profile makes enoxaparin an excellent drug for use in hip fracture patients. Additional trials will be necessary to establish an optimal duration of prophylaxis in this population.

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Arch Intern Med. 2003 Apr 14;163(7):759-68
Management of venous thromboembolism: past, present, and future.
Hyers TM.
Department of Internal Medicine, St Louis University School of Medicine, Care Clinical Research, St Louis, MO 63122, USA. Thyers@careinternet.com

Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, represents a significant source of morbidity and mortality in the United States and worldwide. The pharmacologic management of venous thromboembolic disease has witnessed significant advances since oral anticoagulant and heparin therapies began to gain widespread use more than 50 years ago. Cumulative clinical experience gained from using these 2 classes of antithrombotic agents for the prevention and treatment of venous thromboembolism in high-risk patients pointed to a number of efficacy and safety limitations. This prompted further research and the eventual introduction, in the 1980s, of low-molecular-weight heparin(s) as a potentially superior therapeutic modality. Within the last decade the pace of development of newer classes of antithrombotic agents for venous thromboembolism prevention and treatment (as well as other indications) has accelerated. Among agents at late stages of investigation are ximelagatran (a direct thrombin inhibitor), nematode anticoagulant peptide c2 (a tissue factor VIIa inhibitor), and sodium N-[8(2-hydroxylbenzoyl)amino]caprylate (SNAC)/heparin (a heparin derivative). The most recently approved agents for venous thromboembolism indications include the heparinoid, danaparoid sodium, and the newly introduced selective factor Xa inhibitor, fondaparinux.

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J Vasc Interv Radiol. 2003 Apr;14(4):425-40.
Update on inferior vena cava filters.
Kinney TB.
Department of Radiology, University of California San Diego Medical Center, 200 West Arbor Drive, Mail Code 8756, San Diego, California 92103, USA. tbkinney@ucsd.edu

The ravages of thromboembolic disease continue to plague patients despite improvements in diagnostic imaging and anticoagulation regimens. In certain cases, standard medical therapy for thromboembolism is contraindicated, results in complications, or fails to adequately protect patients from embolic insults. These patients are treated with insertion of inferior vena cava (IVC) filters. Although it appears that IVC filters do reduce long-term pulmonary embolism (PE) rates, there may be a higher associated incidence of IVC thrombosis and lower-extremity deep venous thrombosis (DVT) than with anticoagulation alone. This article will address attributes of the theoretical ideal IVC filter, recently introduced IVC filters, complications of use of IVC filters, and results of recent IVC filter studies. Alternative sites for filter placements are then reviewed, along with use of temporary and retrievable IVC filters and use of IVC filters for prophylactic situations.

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J Vasc Interv Radiol. 2003 Apr;14(4):405-23.
Endovascular management of venous thrombotic and occlusive diseases of the lower extremities.
Sharafuddin MJ, Sun S, Hoballah JJ, Youness FM, Sharp WJ, Roh BS.
Department of Radiology, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, Iowa 52242-1077, USA. mel-sharafuddin@uiowa.edu

Acute complications of deep vein thrombosis (DVT) of the lower extremities include pulmonary embolism and venous ischemia. Delayed complications include a spectrum of debilitating symptoms referred to as postthrombotic syndrome (PST). Anticoagulation therapy is recognized as the mainstay of therapy in acute DVT. However, there are few data to suggest any major beneficial effect on PTS, which is thought to be mediated by valve damage and/or occlusive chronic thrombus and venous scarring. Endovascular catheter-directed thrombolysis techniques with pharmacologic thrombolytic agents, used alone or in combination with mechanical thrombectomy devices, have been proven highly effective in clearing acute DVT, which may allow the preservation of venous valve function and prevention of subsequent venous occlusive disease. Definitive management of underlying anatomic occlusive abnormalities can also be undertaken.

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Am Heart J. 2003 Apr;145(4):614-21.
Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease.
Kleber FX, Witt C, Vogel G, Koppenhagen K, Schomaker U, Flosbach CW; THE-PRINCE Study Group.
Department Internal Medicine, Unfallkrankenhaus, Lehrkrankenhaus der Freien Universitat Berlin, Berlin, Germany. franz-xaverk@ukb.de

BACKGROUND: We compared the efficacy and safety of the low-molecular weight heparin enoxaparin with unfractionated heparin (UFH) for the prevention of venous thromboembolic disease in patients with heart failure or severe respiratory disease. METHODS: This was a multicenter, controlled, randomized, open study in which patients received either enoxaparin (40 mg once daily) or UFH (5000 IU 3 times daily) for 10 +/- 2 days in 64 medical departments in Germany. Patients were stratified and enrolled according to their underlying disease: severe respiratory disease or heart failure. The primary efficacy parameter was a thromboembolic event up to 1 day after the treatment period. RESULTS: Of the 665 patients enrolled, 451 patients were able to be evaluated in the primary efficacy analysis. The incidence of thromboembolic events was 8.4% with enoxaparin and 10.4% with UFH. Enoxaparin was at least as effective as UFH, with a 1-sided equivalence region of -4% (90% CI -2.5-6.5, P =.015). Enoxaparin was associated with fewer deaths, less bleeding, and significantly fewer adverse events (45.8% vs 53.8%, P =.044). CONCLUSIONS: Enoxaparin is at least as effective as UFH in the prevention of thromboembolic events in patients with heart failure or severe respiratory disease. Its beneficial safety profile and once-daily administration is advantageous for inpatient and outpatient use.

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Khirurgiia (Mosk). 2003;(2):6-11.
[Endovascular surgery in prophylaxis of pulmonary thromboembolism and treatment of acute venous thrombosis]
[Article in Russian]
Savel'ev VS, Prokubovskii VI, Kapranov SA.

From 1995 to 2001 1089 patients underwent 1141 endovascular procedures for treatment of acute thrombosis of vena cava inferior (VCI) system and prophylaxis of pulmonary thromboembolism (PT) including 61 catheter thrombectomies from VCI and common iliac veins, 35 regional thrombolyses, 880 implantations of permanent cava-filter "hourglass" and it modifications, 159 implantations of temporary cava-filter "umbrella", 3 implantations of filter-stent, 3 thrombectomies of a giant mobile thrombus with Dotter basket with subsequent cava-filter implantation. Efficacy of PT prophylaxis after these procedures was 97.9%. Catheter thrombectomy and regional thrombolysis permitted to repair passage through deep veins in 69.8% patients. Temporary cava-filter after treatment was removed in 49.1% patients. After implantations of permanent cava-filters early and late complications were seen in 8.9% cases.

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Curr Med Res Opin. 2003;19(1):4-12.
Use of the low-molecular-weight heparin nadroparin during pregnancy. A review.
Makatsaria AD, Bitsadze VO, Dolgushina NV.
Moscow Medical Academy, Russia. dolgushina@mtu-net.ru

Antithrombotic therapy is often used during pregnancy for the treatment and prevention of venous thromboembolism, the prevention of systemic embolism in patients with heart valve prostheses and the prevention of foetal loss in patients with antiphospholipid syndrome. Low-molecular-weight heparins (LMWHs), including nadroparin, have largely replaced unfractionated heparin as the anticoagulant of choice. The use of the LMWH nadroparin in pregnant women at an increased risk of thromboembolism or foetal loss is discussed in this review. Deep vein thrombosis can be effectively treated or prevented with nadroparin without any serious adverse events. Nadroparin 0.1 ml/10 kg s.c. once daily prevents thromboembolic complications in pregnant women with heart valve prostheses. Nadroparin is also effective in preventing foetal loss, through contributing to normal placental development and in decreasing the risk of premature delivery in pregnant women with antiphospholipid syndrome or women with herpes and antiphospholipid syndrome. These results demonstrate nadroparin is effective, easy to administer and associated with a low incidence of foetal and maternal complications. The use of nadroparin at a prophylactic dose of 0.3 ml (2850 IU AXa, 95 IU/kg) (for high-risk patients, 0.3-0.6 ml) s.c. once daily, and a therapeutic dose of 0.1 ml/10 kg (95 IU/kg) s.c. twice daily, is in line with the latest international guidelines of the American College of Chest Physicans.

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Ther Umsch. 2003 Jan;60(1):43-7.
[Anticoagulation in patients with venous thromboembolism]
[Article in German]
Rufer A, Wuillemin WA.
Abteilung fur Hamatologie, Medizinische Klinik, Kantonsspital Luzern.

Deep venous thrombosis and pulmonary embolism are considered to be two variants of one disease--'venous thromboembolism'. Pathogenesis, therapy and prognosis of these both entities are very similar and therefore the term 'venous thromboembolism' has been used in recent literature. The cornerstone of therapy is anticoagulation and initially consists of heparin for at least five days. Because of pharmacokinetic advantages low molecular weight heparins are the therapy of choice. They are as efficient and save as unfractionated heparins and allow weight-adapted dosing with daily subcutaneous injections in most patients. Low molecular weight heparins do not require regularly laboratory monitoring with few exceptions, e.g. renal failure. Therefore outpatient treatment of deep venous thrombosis is possible in most patients. Although there are promising data about outpatient treatment of pulmonary embolism, this is still being studied and can not be recommended outside clinical trials. Introduction of coumarin therapy for venous thromboembolism should be started on day 1 of diagnosis, keeping the total duration of heparin therapy at no more than five days and therefore minimizing the incidence of heparin-induced thrombocytopenia. Evidence from multiple studies indicates that effective coumarin therapy in venous thromboembolism is usually reflected by an INR of 2.0 to 3.0. In patients with massive and hemodynamically relevant thromboembolism alternative therapeutic approaches such as thrombolytic therapy, thrombectomy or insertion of intravenous filters may be useful. Adequately fit compression stockings can reduce the risk of post-thrombotic syndrome after deep venous thrombosis.

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J Vasc Surg. 2003 Mar;37(3):528-32.
Deep venous thrombosis during pregnancy and after delivery: indications for and results of thrombectomy.
Pillny M, Sandmann W, Luther B, Muller BT, Tutschek B, Gerhardt A, Zotz RB, Scharf RE.
Department of Vascular Surgery and Kidney Transplantation, Heinrich Heine University Medical Center, Moorenstrasse 5, 40225 Dusseldorf, Germany. Pillny@med.uni-duesseldorf.de

PURPOSE: Pregnancy and the puerperium are time periods of an increased risk for venous thromboembolism. An ideal treatment should lead to complete restoration of the venous lumen, elimination of the embolic source, and prevention of severe postphlebitic syndrome. Anticoagulation therapy with heparin or thrombectomy are treatment options. In the current literature, these options are discussed controversially. METHODS: From January 1982 to December 2001, 97 women underwent (93% transfemoral) thrombectomy and construction of an arteriovenous fistula (AVF) for deep venous thrombosis related to pregnancy. The clinical and coagulation parameters were evaluated. The AVF was ligated 3 to 6 months later. Follow-up with duplex ultrasound scan, photoplethysmography, and strain-gauge plethysmography was completed in 87 women. RESULTS: Surgery was performed without any maternal death or pulmonary embolization. A cesarean section was carried out during the same anesthesia in 11 cases. Thrombectomy was completed with construction of a temporary AVF in 90 patients (92.8%). One fetal death occurred in the recovery room for unknown reasons. In the early postoperative course, 16 patients (16.5%) underwent redo surgery for rethrombosis with or without the occlusion of the fistula. In 14 of these patients, the venous system remained patent thereafter. Fetal or neonatal death occurred in five cases 2 to 10 weeks after surgery, mainly because of abruption of the placenta probably from anticoagulation. Among 247 preoperatively occluded anatomic regions, 221 could be restored, and the secondary patency rate amounted to 89.5%. After a mean follow-up period of 6 years, 49 patients (56.3%) were seen without a postphlebitic syndrome, and only three patients (3.5%) had had a leg ulcer develop. CONCLUSION: In experienced hands, venous thrombectomy is a safe method to prevent pulmonary embolism and postphlebitic syndrome in women during pregnancy and the puerperium. The frequency of a severe postphlebitic syndrome after our surgical approach is lower than the rates published for anticoagulation treatment alone.

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Chest. 2003 Feb;123(2):399-405.
Acute effects of exercise in patients with previous deep venous thrombosis: impact of the
postthrombotic syndrome.
Kahn SR, Azoulay L, Hirsch A, Haber M, Strulovitch C, Shrier I.
Center for Clinical Epidemiology and Community Studies, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Canada. susan.kahn@mcgill.ca

BACKGROUND: The postthrombotic syndrome (PTS) occurs frequently after deep venous thrombosis (DVT) and is believed to worsen with upright posture and physical activity. However, the effects of exercise in patients with previous DVT have not been studied. STUDY OBJECTIVES: To determine whether previous DVT and PTS limit the ability to exercise, and whether exercise increases the severity of venous symptoms and signs. DESIGN AND SETTING: A repeated-measures cohort study that was conducted at a university-affiliated teaching hospital, 1999-2000. PARTICIPANTS: Subjects with a first episode of unilateral DVT at least 1 year earlier were recruited from the Thrombosis Clinic (total, 41 subjects; with PTS, 19 subjects). INTERVENTION: Treadmill exercise session. Measurements and results: Venous symptoms, calf muscle fatigability, flexibility, and leg volume before and after treadmill exercise were measured and compared. Exercise did not worsen venous symptoms, despite a higher gain in affected leg volume in subjects with PTS vs subjects without PTS (mean difference: affected leg, 53 mL; unaffected leg, -15 mL; p = 0.018). Calf flexibility significantly improved after exercise in subjects with PTS (gastrocnemius: affected-unaffected, PTS vs no PTS + 4.5 degrees, p = 0.0029; soleus: affected-unaffected, PTS vs no PTS + 5.7 degrees, p = 0.0011). CONCLUSIONS: Exercise did not acutely exacerbate symptoms and, in subjects with PTS, resulted in improved flexibility in the affected leg. Our findings suggest that treadmill or similar exercise is unlikely to make symptoms of PTS worse, and may improve flexibility. Further study is indicated to determine whether a regular exercise-training program might have a role in the management of patients with PTS, since, to date, the treatment options for this condition are limited.

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Med Clin North Am. 2003 Jan;87(1):77-110, viii.
DVT prophylaxis and anticoagulation in the surgical patient.
Kaboli P, Henderson MC, White RH.
Division of General Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA.

One of the most common postoperative complications is venous thromboembolism, a term encompassing deep vein thrombosis and pulmonary embolism. This article reviews the epidemiology, natural history, difficulties in diagnosis, and strategies for the prevention of postoperative venous thromboembolism. We thoroughly review the currently available methods for thromboprophylaxis including: early ambulation, elastic compression stockings, pneumatic compression devices, inferior vena cava filters, and a variety of pharmacologic agents such as unfractionated heparin, warfarin, aspirin, low molecular weight heparin, and pentasaccharides. Finally, we review the perioperative management of patients on long-term oral anticoagulation.

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Rev Cardiovasc Med. 2002;3 Suppl 2:S61-7.
Quality-of-life improvement using thrombolytic therapy for iliofemoral deep venous thrombosis.
Comerota AJ.
Jobst Vascular Center, Toledo, Ohio, USA.

Patients with iliofemoral deep venous thrombosis suffer the most severe postthrombotic morbidity. Techniques that effectively remove thrombus from the venous system eliminate venous obstruction and potentially preserve valvular function. This will likely reduce or avoid the postthrombotic syndrome and improve long-term quality of life. To evaluate whether catheter-directed thrombolysis is associated with improved quality of life compared with anticoagulation alone and whether outcome in the thrombolysis group is related to lytic success, 98 patients with iliofemoral deep venous thrombosis who were treated at least 6 months earlier were identified and queried with a validated health-related quality-of-life questionnaire. Sixty-eight patients were identified through the Venous Registry (a national, multicenter venous registry) and were treated with catheter-directed thrombolysis with urokinase, and 30 patients were identified by means of medical record review and were treated with anticoagulation alone. All patients were candidates for thrombolysis; however, the treatment decision was made according to physician preference. The two treatment groups did not differ significantly in average time between the reference hospitalization and first contact. No difference was found in physical functioning and well-being between the groups before the development of deep venous thrombosis. Following treatment, patients receiving catheter-directed thrombolysis reported better overall physical functioning, less stigma, less health distress, and fewer postthrombotic symptoms compared to those patients treated with anticoagulation alone. Within the thrombolysis group, successful lysis correlated with health-related quality of life. Catheter-directed thrombolysis for the management of patients with iliofemoral deep venous thrombosis significantly improves health-related quality of life compared to similar patients treated with anticoagulation alone. Improved quality of life is related to successful thrombolysis. These data offer a compelling argument for a prospective randomized study.

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Rev Cardiovasc Med. 2002;3 Suppl 2:S53-60.
Thrombolytic therapy for acute deep vein thrombosis and the venous registry.
Meissner MH.
Department of Surgery, University of Washington School of Medicine, Seattle, WA, USA.

Randomized clinical trials have defined anticoagulation with unfractionated or low molecular weight heparin followed by warfarin as standard therapy for acute deep venous thrombosis (DVT). Such treatment is highly effective in preventing recurrent venous thromboembolism, but provides imperfect protection against development of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, catheter-directed thrombolytic therapy potentially affords an improved long-term outcome in selected patients with DVT. A national venous registry, compiling data from 63 participating centers, was established to collect data regarding the technical details of the procedure and early outcome. Data from the registry have established the optimal technical approach and patient population. An antegrade catheter-directed approach using urokinase in patients with acute iliofemoral DVT of less than 10 days duration and no prior history of DVT may achieve complete lysis in 65% of patients. Analysis of the clinical outcome is pending, but early results suggest improved valve function and fewer symptoms at 1 year in patients with complete thrombolysis. These promising data should serve as the basis for future randomized trials of catheter-directed thrombolysis for the treatment of acute DVT.

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J Cardiol. 2002 Dec;40(6):267-73.
[Clinical experience with retrievable vena cava filters for prevention of pulmonary thromboembolism]
[Article in Japanese]
Ishikura K, Yamada N, Oota M, Yazu T, Nakamura M, Isaka N, Nakano T.
First Department of Internal Medicine, Mie University School of Medicine, Mie.

OBJECTIVES: To evaluate the feasibility, effectiveness and complications of the retrievable vena cava filter [Guther tulip vena cava filter(GTF)] for the prevention of pulmonary thromboembolism in patients with deep vein thrombosis. METHODS: Seventeen patients, 3 males and 14 females, aged 21 to 82 years (mean age 59 +/- 19 years), underwent implantation of GTFs between December 2000 and February 2002 at Mie University Hospital. All patients were treated under diagnoses of deep vein thrombosis with or without pulmonary thromboembolism based on venous ultrasonography, venography or computed tomography. Eleven patients were treated with thrombolysis. RESULTS: Significant thromboembolus was trapped within the filter in 3 of 12 patients. No acute pulmonary thromboembolism occurred during implantation or at retrieval of the GTF. Retrieval of the GTF was attempted in 9 patients, and 8 GTFs were retrieved successfully. Mean interval of the filter implantation was 13.4 +/- 6.3 days and the mean retrieval time was 4.8 +/- 3.2 min. No complications occurred except for one case of minor hemorrhage at the puncture site. CONCLUSIONS: The placement and retrieval of the retrievable vena cava filter was feasible and safe. This filter was also effective for the prevention of pulmonary thromboembolism. This retrievable vena cava filter may be a good first-choice filter for both permanent and temporary use.

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Curr Opin Pulm Med 2002 Sep;8(5):383-8

Fixed-dose versus adjusted-dose low molecular weight heparin for the initial treatment of patients with deep venous thrombosis.

Harenberg J.

4th Department of Medicine, University Hospital Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany. j-harenberg@t-online.de

Patients with acute deep vein thrombosis (DVT) were treated with a body-weight independent dosage of 2 x 8000 aXa IU low-molecular-weight heparin (LMWH) Certoparin. After the subcutaneous administration of 8000 IU Certoparin, pharmacodynamic parameters did not differ between patients and healthy volunteers, and the AUC of the anticoagulant effects were not related to body weight. Two clinical trials demonstrated a greater regression of thrombi and a lower occurrence of recurrent venous thromboembolism (VTE), major bleeding, and mortality within 14 days of initial therapy compared with intravenous heparin. D-dimer decreased, and anti-Xa activity increased in those patients with a regression of thrombosis. The benefit of the reduced occurrence of recurrent VTE, major bleeding, and mortality was maintained up to 6 months. Major bleeding was not related to the body weight in either treatment group. Treatment of acute DVT in adults with fixed dose of 2 x 8000 aXa IU LMWH Certoparin is more effective and safer than heparin.

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Eur J Vasc Endovasc Surg 2002 Sep;24(3):209-14

Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis.
A randomised clinical trial.

Elsharawy M, Elzayat E.

Ismailia POB 262, Ismailia 41511, Egypt.

OBJECTIVE: catheter directed thrombolysis has been advocated for complete and rapid dissolution of iliofemoral deep venous thrombosis (DVT). The aim of our study is to compare, in a randomised trial, local thrombolysis and anticoagulation with anticoagulation alone in patients with iliofemoral DVT. METHODS: a consecutive series of 35 eligible patients, were randomised to either catheter directed thrombolysis followed by anticoagulation or to anticoagulation alone. Clot lysis and deep venous reflux were assessed with ultrasound duplex and plethysmography after 6 months. RESULTS: complete data were available in the 18 and 17 patients randomised to thrombolysis and anticoagulation, respectively. At 6 months, patency rate was better in cases treated with thrombolysis [13/18 (72%) vs 2/17 (12%), p < 0.001]. Venous reflux was higher in-patients treated with anticoagulant [7 patients (41%) vs 2 (11%), p = 0.04]. CONCLUSION: in the short-term patients treated with catheter directed thrombolysis obtained better patency and competence than those treated with standard anticoagulation.

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Curr Opin Pulm Med 2002 Sep;8(5):389-93

Bed rest versus ambulation in the initial treatment of patients with proximal deep vein thrombosis.

Partsch H.

Wilhelminen Hospital, Vienna, Austria. Hugo.Partsch@univie.ac.at

A large number of trials have shown that many patients with venous thromboembolism can be treated as outpatients by using low molecular weight heparin. However, the amount of physical activity is neither mentioned in the study protocols nor in the instruction brochures, which are given to the patients. In most institutions, the fear of dislodging clots by ambulation is more common than the consideration of thrombus propagation and of recurrence; therefore, bed rest is recommended at least for the initial stage. There have been two randomized trials showing that bed rest as a part of the initial treatment of patients with deep vein thrombosis (DVT) is not able to substantially reduce the incidence of pulmonary emboli detected by repeat lung scanning. In one study performed in patients with proximal DVT, it could be demonstrated that leg compression and walking exercises are able to reduce edema and pain more rapidly and more effectively than bed rest. Progression of the thrombus size assessed by an independent Duplex examiner was statistically significantly greater in those patients confined to bed when compared with ambulatory patients with compression therapy. By counteracting against venous stasis, walking exercises and compression therapy have an important impact on the clinical outcome and should therefore be addressed in future studies.

Hamostaseologie 2002 Aug;22(3):25-9

[Ximelagatran for treatment of venous thromboembolism]

[Article in German]

Harenberg J, Fenyvesi T, Jorg I.

IV. Medizinische Klinik, Universitatsklinikum, Mannheim, Germany.

Acute venous thromboembolism including asymptomatic and symptomatic pulmonary embolism without respiratory or cardiac failure is currently treated for 6 months, initially with subcutaneous low-molecular-weight heparin followed by oral anticoagulation. The main drawback of oral anticoagulation is caused by severe bleeding complications. Oral Ximelagatran has shown to be as effective and safe for the initial treatment of acute deep venous thrombosis compared to subcutaneous low-molecular-weight heparin followed by oral warfarin over a period of 4 weeks. Currently, oral ximelagatran is investigated versus subcutaneous low-molecular-weight heparin and oral warfarin over 6 months to demonstrate an almost equal efficacy and safety. The study is performed on a double blind and double dummy basis. Six months after oral anticoagulation of patients with acute deep venous thrombosis, recurrent venous thromboembolism may occur in up to 25% within 2 years. Ximelagatran is currently investigated versus placebo to demonstrate a reduced recurrence rate of venous thromboembolism over a period of 18 months.

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N Engl J Med 2002 Sep 5;347(10):726-30

Use of the low-molecular-weight heparin reviparin to prevent deep-vein thrombosis after leg injury requiring immobilization.

Lassen MR, Borris LC, Nakov RL.

Department of Orthopedics, Hillerod Hospital, Hillerod, Denmark. mirula@fa.dk

BACKGROUND: Deep-vein thrombosis is a well-recognized complication after trauma to the legs and subsequent immobilization, but there are no generally accepted approaches to preventing this complication. METHODS: We performed a prospective, double-blind, placebo-controlled trial to evaluate the efficacy and safety of subcutaneous reviparin (1750 anti-Xa units given once daily) in 440 patients who required immobilization in a plaster cast or brace for at least five weeks after a leg fracture or rupture of the Achilles tendon. The study drug was given throughout the period of immobilization. Venography of the injured leg was performed within one week after removal of the plaster cast or brace, or earlier if there were symptoms suggesting deep-vein thrombosis. RESULTS: Data on efficacy and end points were available for 371 patients. Deep-vein thrombosis was diagnosed in 17 of the 183 patients randomly assigned to receive reviparin (9 percent) and in 35 of the 188 patients randomly assigned to receive placebo (19 percent) (odds ratio, 0.45; 95 percent confidence interval, 0.24 to 0.82). Most of the thromboses were distal (14 in the reviparin group and 25 in the placebo group). There were two cases of pulmonary embolism, both in patients in the placebo group who also had proximal deep-vein thrombosis. There were no differences between the two groups with respect to bleeding or other adverse events. CONCLUSIONS: Deep-vein thrombosis is common in persons with leg injury requiring prolonged immobilization. Reviparin given once daily appears to be effective and safe in reducing the risk of this complication. Copyright 2002 Massachusetts Medical Society

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J Obstet Gynaecol Can 2002 Jul;24(7):568-71

Use of low molecular weight heparin in acute venous thromboembolic events in pregnancy.

Malcolm JC, Keely EJ, Karovitch AJ, Wells PS.

University of Ottawa, Ottawa, ON, Canada.

OBJECTIVE: To compare the maternal and neonatal outcomes arising from the use of low molecular weight heparin (LMWH) or unfractionated heparin (UFH) in the treatment of acute venous thromboembolism (VTE) in pregnancy. STUDY DESIGN: A retrospective review of the charts of all women treated for acute VTE in pregnancy at the Ottawa Hospital from January 1990 to December 1999. RESULTS: Twenty-three cases were identified, of which 11 were treated with LMWH and 12 with UFH. Maternal and fetal outcomes were similar between the two groups. Hospital length of stay was shorter in the LMWH group. There was no difference in delivery management between the two groups. There was minor bleeding in 2 women in the UFH group and none in the LMWH group. There was one recurrent VTE during treatment in each of the groups.CONCLUSION: There is no difference in complication rate between LMWH and UFH in the treatment of acute VTE in pregnancy.

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Arch Intern Med 2002 Sep 9;162(16):1833-40

Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies.

Turpie AG, Bauer KA, Eriksson BI, Lassen MR.

Department of Medicine, Hamilton Health Sciences-General Hospital, 237 Barton, Hamilton, Ontario, Canada L8L 2X2. turpiea@mcmaster.ca

BACKGROUND: Orthopedic surgery remains a condition at high risk of venous thromboembolism (VTE). Fondaparinux, the first of a new class of synthetic selective factor Xa inhibitors, may further reduce this risk compared with currently available thromboprophylactic treatments. METHODS: A meta-analysis of 4 multicenter, randomized, double-blind trials in patients undergoing elective hip replacement, elective major knee surgery, and surgery for hip fracture (N = 7344) was performed to determine whether a subcutaneous 2.5-mg, once-daily regimen of fondaparinux sodium starting 6 hours after surgery was more effective and as safe as approved enoxaparin regimens in preventing VTE. The primary efficacy outcome was VTE up to day 11, defined as deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism. The primary safety outcome was major bleeding. RESULTS: Fondaparinux significantly reduced the incidence of VTE by day 11 (182 [6.8%] of 2682 patients) compared with enoxaparin (371 [13.7%] of 2703 patients), with a common odds reduction of 55.2% (95% confidence interval, 45.8% to 63.1%; P<.001); this beneficial effect was consistent across all types of surgery and all subgroups. Although major bleeding occurred more frequently in the fondaparinux-treated group (P =.008), the incidence of clinically relevant bleeding (leading to death or reoperation or occurring in a critical organ) did not differ between groups. CONCLUSION: In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily, starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.

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Issues Emerg Health Technol 2002 Aug;(37):1-4

Fondaparinux for post-operative venous thrombosis prophylaxis.

Garces K.

Fondaparinux (Arixtra TM ) belongs to a new class of synthetic antithrombotic agents called pentasaccharides. It was recently approved in Canada for the prevention of venous thromboembolic events (VTE) in patients undergoing orthopedic surgeries of the lower limbs such as hip fracture, knee surgery and hip replacement surgery. Fondaparinux was more efficacious in three of four phase III trials comparing fondaparinux and enoxaparin for the prevention of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in patients undergoing major orthopedic surgery. However, there was no difference in the incidence of pulmonary embolism (PE) between the two treatment groups in any of the four trials. The overall major bleeding rate associated with fondaparinux was higher than the rate associated with enoxaparin, although the statistical significance of this difference is inconsistent.

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Can J Surg 2002 Aug;45(4):282-7

Heparin prophylaxis for deep venous thrombosis in a patient with multiple injuries: an evidence-based approach to a clinical problem.

Hill AB, Garber B, Dervin G, Howard A.

Surgical Epidemiology Rounds, Ottawa Hospital, University of Ottawa, Ont. ahill@ottawahospital.on.ca

OBJECTIVE: To demonstrate a clinical decision-making process by which to determine if heparin prophylaxis for deep venous thrombosis (DVT) is appropriate in a specific patient with multiple injuries. DATA SOURCES: A Medline search of the literature. Search terms included trauma, heparin, deep venous thrombosis, thrombophlebitis, phlebitis, and trauma. STUDY SELECTION: Eleven studies were selected from 789 publications using published criteria. Incidence, risk and potential for prophylaxis were established through a structured review process. DATA EXTRACTION: After the structured review, a small number of studies were available for the consideration of incidence (2), natural history (4) and prophylactic therapy (2). DATA SYNTHESIS: The incidence of DVT in a patient with such multiple injuries is significant (58%-63%). The resulting risk of pulmonary embolism was 4.3% with an associated 20% death rate. Prophylaxis with low molecular weight heparin is associated with a statistically and clinically significant risk reduction for DVT when compared with unfractionated heparin and untreated controls. CONCLUSIONS: Few of the multiple available studies concerning trauma, DVT and pulmonary embolism meet reasonable standards to establish clinical validity. Available guidelines for literature evaluation allow surgeons to select relevant articles for consideration. Patients with multiple trauma appear to be at significant risk for DVT. The death rate associated with subsequent pulmonary embolism is significant. There is reasonably good evidence to suggest that low molecular weight heparin will reduce this likelihood without a significant risk of treatment complications.

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Curr Opin Pulm Med 2002 Sep;8(5):394-7

Current controversies in deep vein thrombosis prophylaxis after orthopaedic surgery.

Dahl OE, Bergqvist D.

Department of Orthopaedics and Research Forum, Ullevaal University Hospital, Oslo, Norway. oladahl@start.no

As a result of easy measurable perioperative bleeding and a high number of subclinical deep vein thromboses after surgery, total hip replacement has become a benchmark for antithrombotic drug development. Today, a nonscientific evidence-based transatlantic view on thromboprophylaxis in orthopaedic surgery exists. Efforts should be taken to bridge these divergent opinions. We need to standardize study designs that allow unbiased comparison and aggregation of data to get insight in rare complications like the cauda equina syndrome associated with spinal analgesic techniques and anticoagulation and to optimize thromboprophylaxis in homogeneous groups of patients. Dosage, timing of initiation in relation to surgery, and duration of prophylaxis seems a crucial and open question for all homogeneous groups of orthopaedic patients. A definition on surgical bleeding, which allows practical measurement procedures and quantification, is lacking. Clinical studies on vascular endpoints are warranted to achieve relevant basic data for health economic analyses, which also lack scientific standardized procedures. An intercontinental close cooperation is needed to solve these issues.

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Curr Opin Pulm Med 2002 Sep;8(5):372-8

Travel and venous thrombosis.

Gallus AS, Goghlan DC.

Department of Hematology, Flinders Medical Center, Adelaide, Australia. alexander.gallus@flinders.edu.au

Debate continues about whether and to what extent travel predisposes to venous thrombosis and pulmonary embolism (PE). Almost certainly, the strength of any association was greatly exaggerated in recent press reports. Conclusions from case-control studies vary, with some finding no excess of recent travel among patients with venous thromboembolism and others reporting a two-four fold excess. The strongest evidence that prolonged air travel predisposes to thrombosis comes from the travel history of people who present with PE immediately after landing. Two independent analyses suggest that the risk of early embolism increases exponentially with travel times beyond 6 hours and may reach 1:200,000 passengers traveling for more than 12 hours. The most likely explanation is venous stasis in the legs from prolonged sitting, and there is evidence (preliminary and controversial) that elastic support stockings may prevent deep vein thrombosis in people who travel long-distances. There is an urgent need for more and better studies to define the absolute hazard from travel-related thrombosis and the personal risk factors that may contribute. Without these, it is difficult to give a balanced account to people who intend to travel or to consider definitive prevention trials. Case reports suggest that in most cases, travel-related thrombosis has affected people who were also at risk because of previous thrombosis, recent injury, or other predispositions. This makes it sensible to target such "at risk" people with advice about hazards and precautions, at least until formal study validates some other approach.

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Cardiol Rev 2002 Jul-Aug;10(4):249-59

Treatment of venous thromboembolism.

Nazario R, Delorenzo LJ, Maguire AG.

Division of Pulmonary and Critical Care Medicine New York Medical College, Valhalla, New York, USA.

Venous thromboembolism (VTE), comprised of pulmonary embolism (PE) and deep vein thrombosis (DVT), is a disease entity with a significant morbidity and mortality. Anticoagulation, initially with intravenous heparin and followed with long term warfarin treatment is the traditional therapy for VTE. Low molecular weight heparin, (LMWH) has a greater bioavailability than unfractionated heparin and can be administered subcutaneously. LMWH has resulted in shorter hospitalizations, reduced inicidents of major bleeding complications, and has moved the treatment of VTE for selected patients to the out-patient setting. Thrombolytic therapy has been recommended in patients with life threatening PE such as those with right ventricular dysfunction or hypotension. There are advances in the technology for clot removal with catheter embolectomy and clot fragmentation. Inferior vena cava filters can be place percutaneously in patients who are at high risk for VTE or those in whom anticoagulation is contraindicated. Since VTE is often asymptomatic, prevention is the most effective means to reduce morbidity and mortality.

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Pharmacoeconomics 2002;20(9):603-15

Direct medical cost of managing deep vein thrombosis according to the occurrence of complications.

O'Brien JA, Caro JJ.

Caro Research Institute, Concord, Massachusetts 01742, USA. jobrien@caroresearch.com

BACKGROUND: Management of deep vein thrombosis (DVT) has evolved from hospitalisation for intravenous heparin therapy to treatment options that include acute management as an outpatient. While efficacy and safety remain the principal basis for choosing a therapy, the economic consequences of that choice should be considered as well. OBJECTIVE: To estimate the average cost of various DVT management options from the perspective of US health payers. DESIGN: Inpatient and outpatient management strategies were examined. Inpatient cases were identified by International Classification of Diseases, 9(th) Edition, Clinical Modification codes and were classified into subgroups according to complication status. A cost estimate was developed by applying unit costs to the corresponding course of treatment. Cost estimates included initial acute care and that occurring in the following 6 months. Resource use profiles and unit costs were derived from several statewide inpatient, emergency room and ambulatory care databases supplemented by national fee schedules, published reports and peer-reviewed literature. All costs are reported in 1999 US dollars. RESULTS: The mean 6-month treatment costs for inpatient management ranged from US dollars 3906 to US dollars 17,168, depending on complication status. For outpatient management, the cost ranged from US dollars 2394 to US dollars 3369, depending on frequency of low molecular weight heparin (LMWH) injection and need for professional assistance. CONCLUSIONS: The management strategy selected for DVT has an important economic impact. Self-administered LMWH in a homecare setting results in the lowest cost. However, as some patients either cannot, or will not, be treated this way, it is important for decision makers to consider the costs of other strategies.

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Pharmacoeconomics 2002;20(9):593-602

Cost effectiveness of tinzaparin sodium versus unfractionated heparin in the treatment of proximal deep vein thrombosis.

Caro JJ, Getsios D, Caro I, O'Brien JA.

Caro Research Institute, Concord, Massachusetts 01742, USA. jcaro@caroresearch.com

OBJECTIVE: To evaluate economic and health implications of tinzaparin sodium, a once a day low-molecular-weight heparin (LMWH), versus unfractionated heparin (UFH) in the treatment of acute deep vein thrombosis (DVT) from a US healthcare payer perspective. STUDY DESIGN: An economic model, composed of two submodules, was created: A short-term module based on clinical trial data covering the first 3 months and a long-term module that projects trial results based on published data for up to 50 years. METHODS: Clinical trial results were combined with data from long-term follow-up studies of DVT in a model that estimates the health and economic consequences of treatment. Both short- and long-term costs with tinzaparin sodium were compared with UFH, as were health outcomes and quality-adjusted life-years (QALYs). RESULTS: Patients treated with tinzaparin sodium are estimated to live a mean of 0.9 years longer on average (0.6 discounted), resulting in an increase of 0.8 QALYs (0.5 discounted). At the same time, lifetime savings are US dollars 621 per patient (1999 values), even when all patients receiving tinzapirin sodium are treated as inpatients. Early discharge of patients receiving tinzaparin sodium, or outpatient treatment, would save between US dollars 3000 and US dollars 5000 per patient. CONCLUSION: Tinzaparin sodium leads to better health outcomes and substantial economic savings compared with UFH treatment when all management costs are considered.

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J South Orthop Assoc 2000 Fall;9(3):182-6

Patient compliance and satisfaction with mechanical devices for preventing deep venous thrombosis after joint replacement.

Robertson KA, Bertot AJ, Wolfe MW, Barrack RL.

Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA.

A consecutive series of patients having total joint arthroplasty at a single university hospital were sequentially treated with two mechanical devices for prevention of deep venous thrombosis (DVT). The first 104 patients (group 1) wore thigh-high sequential compression device (SCD). The next 120 patients (group 2) wore a foot pump. Daily documentation of hourly compliance with each respective device was recorded until discharge. A patient satisfaction questionnaire was also obtained. Patient understanding about the devices' function aided compliance (73% compliance in group 1, and 77% in group 2). The satisfaction questionnaire revealed significantly greater satisfaction in group 2 (73%) versus group 1 (55%). Of a subgroup of 35 patients who had used both devices, 24 preferred the foot pump, 7 the SCD, and 4 had no preference. This study showed a higher degree of compliance and satisfaction for foot pumps as prophylaxis against DVT.

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J Cardiovasc Surg (Torino) 2002 Aug;43(4):495-500

Low molecular weight heparins in the long-term treatment of venous thromboembolism.

Liapis CD, Daskalopoulos ME, Daskalopoulou SE.

2nd Department of Propedeutic Surgery, Athens University Medical School, Laiko Hospital, Greece.

Low molecular weight heparins (LMWHs) have extensively replaced unfractionated heparin (UFH) in both thromboprophylaxis and initial treatment of venous thromboembolism (VTE) and their use for such indications is now well established. This paper reviews the role of LMWHs in the long-term treatment of VTE. Venous thrombosis, although a very frequent occurrence in everyday practice, still remains controversial in its treatment. Available literature comparing different LMWHs with UFH and oral anticoagulants (OAs) is presented. Comparison and evaluation of the effectiveness, safety and costs of alternative treatments are also made. The differences of various LMWHs are discussed and the need for separate clinical trials for every single LMWH is highlighted.

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Chest 2002 Jul;122(1):108-14

Management of acute proximal deep vein thrombosis: pharmacoeconomic evaluation of outpatient treatment with enoxaparin vs inpatient treatment with unfractionated heparin.

Spyropoulos AC, Hurley JS, Ciesla GN, de Lissovoy G.

Clinical Thrombosis Center, Lovelace Health Systems, Albuquerque, NM 87108, USA. acspyr@lovelace.com

OBJECTIVES: A landmark Canadian randomized controlled clinical trial compared treatment of acute proximal vein thrombosis via low-molecular-weight heparin (LMWH) [enoxaparin] administered primarily at home with IV unfractionated heparin (UH) in the hospital. Results demonstrated equivalent safety and efficacy for home care with enoxaparin with a reduction in cost. Our objective was to validate these findings in the routine practice setting of a US health maintenance organization. DESIGN: Retrospective analysis of medical and administrative records of health-plan members meeting inclusion-exclusion criteria of the Canadian trial during the period from 1995 to 1998. SETTING: Staff-model health maintenance organization serving New Mexico. PATIENTS:Persons presenting as outpatients from 1995 to 1996 or from 1997 to 1998 with acute, proximal deep vein thrombosis (DVT) diagnosed by duplex ultrasonography. INTERVENTIONS: Initial anticoagulant therapy of IV UH administered in the hospital (from 1995 to 1996 group, n = 64) or subcutaneous LMWH (enoxaparin) administered primarily at home (from 1997 to 1998 group, n = 65), followed by warfarin therapy. RESULTS: No statistically significant differences were observed in the number of recurrent venous thromboembolic events (p = 0.36) or bleeding events (p = 1.0). Mean +/- SD cost per patient was 9,347 dollars +/- 8,469 in the enoxaparin group compared with 11,930 dollars +/- 10,892 in the UH group, a difference of - 2,583 dollars (95% bootstrap-adjusted asymmetrical confidence interval, - 6,147 dollars, + 650 dollars). CONCLUSIONS: Retrospective replication of the Canadian study in a US routine (managed) care setting found similar clinical and economic outcomes. Treatment of acute proximal DVT with enoxaparin in a primarily outpatient setting can be accomplished safely and yields savings through avoidance or minimization of inpatient stays.

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J Crit Care 2002 Jun;17(2):95-104

Venous thromboembolism and its prevention in critical care.

Geerts W, Cook D, Selby R, Etchells E.

Department of Medicine and Health Policy, University of Toronto, Toronto, Canada.

BACKGROUND: Evidence-based guidelines for the prevention of venous thromboembolism (VTE) are available for most major surgical and medical patient groups. Such guidelines have not been established for critically ill patients. OBJECTIVE: To perform a systematic review of the prevalence of deep vein thrombosis (DVT), the efficacy of thromboprophylaxis, and the rates of thromboprophylaxis use in critically ill patients. METHODS: Computerized literature search for relevant studies meeting prespecified criteria. RESULTS: The rates of objectively confirmed DVT in 4 prospective studies ranged from 13% to 31%. We identified only 3 randomized trials (1 in abstract form) of thromboprophylaxis in critical care unit patients. These studies show the efficacy of low-dose heparin and low molecular weight heparin compared with no prophylaxis; however, we found no trials comparing these 2 interventions. Eleven compliance studies reported that some form of thromboprophylaxis was used in 33% to 100% of critically ill patients, although only 1 study addressed the issue of appropriate prophylaxis use. CONCLUSIONS: Data on the epidemiology of VTE and its prevention in critically ill patients are very limited. Further research is needed to better define patient risk factors for VTE, optimal methods of thromboprophylaxis, and strategies to improve compliance with prophylaxis recommendations. In the meantime, prevention strategies, shown to be effective in other related patient groups, and general principles of individual pharmacotherapy should guide the routine use of prophylaxis during critical illness. Copyright 2002, Elsevier Science (USA). All rights reserved.

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S Afr J Surg 2002 Feb;40(1):15-6

Should knee-length replace thigh-length graduated compression stockings in the
prevention of deep-vein thrombosis?

Hameed MF, Browse DJ, Immelman EJ, Goldberg PA.

Colorectal and Vascular Surgery Units, Department of Surgery, Groote Schuur Hospital, University of Cape Town.

OBJECTIVE: To compare knee-length with thigh-length graduated compression stockings for correct application and rate of compliance when they are prescribed for the prevention of deep-vein thrombosis in surgical patients. METHODOLOGY: Patients who were prescribed graduated compression stockings were prospectively studied in three surgical units at Groote Schuur Hospital from February to June 1997. Knee-length stockings were prescribed in the colorectal unit, while the thigh-length variety were prescribed in the hepatobiliary and trauma units. Patients were observed for the correct application and size of stockings, and the presence of compression bands. A total of 72 patients were studied. RESULTS: One patient in the knee-length group and 7 patients in the thigh-length group were not wearing their stockings. Twenty-one of 30 patients (70%) in the knee-length group and 15 of 42 (35.7%) in the thigh-length group had correctly applied stockings (P = 0.009). CONCLUSIONS: Knee-length are more likely to be correctly applied than thigh-length stockings. Knee-length should replace thigh-length stockings in general surgical patients.

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Tidsskr Nor Laegeforen 2002 Apr 20;122(10):1012-6

[Warfarin treatment of venous thromboembolism]

[Article in Norwegian]

Andersen IA, Hammerstrom J.

Det medisinske fakultet Medisinsk teknisk forskningssenter 7489 Trondheim. ingridan@stud.ntnu.no

BACKGROUND: Warfarin treatment of venous thromboembolism is the most frequent cause of reported serious and fatal adverse events associated with drug therapy in Norway. We assessed quality of treatment during transfer from hospital to community-based care. MATERIAL AND METHODS: 66 out of 100 consecutive patients with venous thromboembolism were studied by a retrospective survey that included data from hospital records and a questionnaire survey. RESULTS: Time in therapeutic range was 57% during the first four weeks. Undertreatment was the most frequent deviation. Some patients reported a long time lag from INR measurement to dose prescription in community care; 42% did not receive written treatment information. There were six recurrences, but no serious or fatal bleeding complications during one year of observation. Patient satisfaction with information and treatment organisation was high. INTERPRETATION: There is room for improvement of patient information and treatment quality in outpatient care in our area.

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Harefuah 2002 May;141(5):424-9, 499

[Local thrombolysis for the treatment of patients with proximal deep vein thrombosis of the leg]

[Article in Hebrew]

Lieberman S, Safadi R, Aner H, Verstandig A, Sasson T, Bloom AI.

Departments of Radiology, Internal Medicine and Vascular Surgery, Hadassah University Hospital, Ein-Kerem, Jerusalem, Israel.

BACKGROUND: Standard anticoagulatn therapy for lower extremity DVT does not distinguish between proximal and distal veins. Catheter directed thrombolytic therapy is a new emerging aggressive option for suitable patients with proximal DVT. OBJECTIVES: Review of the literature and presentation of two patients in whom the procedure was successfully performed. PATIENTS AND METHODS: Two patients with lower extremity DVT involving the iliac and femoral veins were treated with catheter directed urokinase infusion in addition to conventional anticoagulant therapy. In both cases underlying venous stenoses were identified and treated by balloon angioplasty and insertion of metallic stents. Thrombolytic therapy was continued for 36-60 hours at a rate of 100,000 units per hour. RESULTS: Significant clinical and radiological improvement was obtained in both patients with restoration of centripetal venous flow in the deep venous system. No significant complication occurred. A persistent clinical benefit was seen at follow-up of 8 and 24 months respectively. CONCLUSIONS: Catheter directed thrombolytic therapy should be considered as adjuvant therapy for patients with acute proximal lower extremity DVT, in whom there are no contraindications. Underlying venous stenoses should be dilated and stented if necessary. Early restoration of venous flow results in rapid clinical improvement and may prevent the future development of post thrombotic syndrome.

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J Vasc Nurs 2002 Jun;20(2):53-9

Deep vein thrombosis prophylaxis: the effectiveness and implications of using below-knee or thigh-length graduated compression stockings.

Byrne B.

The Alfred Hospital in Melbourne, Australia.

Potential complications of reduced mobility in both acute and chronically ill patients continue to challenge nurses on a daily basis. Deep vein thrombosis (DVT) is one of the most serious of these complications. Graduated compression stockings, also known as antiembolism stockings, are among the most commonly available and accepted methods of external compression for the prophylaxis of DVT. Currently, there are 2 lengths of graduated compression stockings in common use, thigh-length and below-knee. Although thigh-length stockings are widely perceived to be more effective in prophylaxis, difficulties associated with therapeutic application and maintenance are often encountered in different clinical settings. Below-knee stockings are easier to apply and maintain and appear to be tolerated better by patients. The aim of this article is to examine existing support for both lengths of stockings in terms of their effectiveness in DVT prophylaxis and to discuss the implications for practice.
   

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